Helena Cassadine first arrived in Port Charles after her husband, Mikkos', plan to freeze the world was foiled by Luke and Laura Spencer and Mikkos was killed. She wanted revenge on the Spencers and put a curse on them on their wedding day and then disappeared.
She returned in late 1997 after Alexis discovered that she was really Natasha Cassadine, Mikkos' illegitimate daughter. Upset over Mikkos' infidelity, Helena took it out on Alexis, who was very much afraid of Helena. Alexis remembered that when she was a little girl, she had witnessed Helena slit the throat of her mother. Helena had also returned to get her hands on the Cassadine fortune. To do this, she needed control over the heir to the fortune, her grandson Nikolas. But her son Stefan stood in her way because Stefan had way more influence over Nikolas than Helena could muster. So she made moves to distract Stefan away from Nikolas using his obsession with Laura Spencer.
In her cat and mouse games with Alexis, she made Alexis defend Tony Jones when he kidnapped Michael Corinthos III. This move effectively ended Alexis' relationship with Ned and got her fired from ELQ. But Alexis retaliated by aligning with Luke Spencer in a plot to kill Helena. Luke loosened the railing of the parapet so that when Helena was lured onto it she would fall to her death. But Katherine Bell became the victim instead. Luke and Alexis then attempted to frame Helena for Katherine's murder. They even got Helena arrested, but it turned out that Helena had saved Katherine after the fall (for her own purposes of course) so the charges were dropped.
With Katherine in her debt, Helena used her to break apart the bond between Stefan and Nikolas. Katherine seduced Nikolas, upsetting Stefan and Laura. But a different scandal was about to bust wide open. Luke had managed to discover evidence that Stefan was Nikolas' real father, which meant that Nikolas was not the Cassadine prince/heir and the fortune was up for grabs. Luke told Alexis who decided to go after her share of the fortune, beginning her crusade by announcing the paternity news publicly. This created animosity between Nikolas and Laura as well as Stefan and Alexis.
Pleased, Helena went after the Cassadine estate and a judge named her executor, much to everyone else's surprise. But Alexis smelled something fishy involving a secret deal between Helena and Dr. Lastiris. Alexis paired up with Jax to find out what the deal was. Helena had the doc killed before Alexis could get to him, so Alexis and Jax decided to go after Nikolas' medical records in the hope that the secret would be in them. Helena tried to stop them by having them held at gunpoint. However the duo escaped with the records and ran off to catch her. She led them into the Sahara where their faulty helicopter crashed and she left them there to die, satisfied that her secret was safe. But they were rescued by Ned, Jerry Jacks, and V Androwski. Alexis then realized that she loved Ned enough to drop her pursuit of the Cassadine fortune, which pleased Helena.
Helena then began making plans to get rid of Stefan and Laura, who had bonded and grown closer over their son Nikolas. However, Stefan noticed Helena's fixation on Laura and poisoned her. The effects of the drug left Helena mute and paralyzed, and Stefan gleefully brought his completely dependent mother back to Wyndemere. But she still comprehended everything going on. What no one realized was that Helena had a partner in crime, Cesar Faison. They had already plotted to kidnap and brainwash Lucky Spencer and Faison was eager to continue. So he found an antidote and gave it to Helena, but it didn't work. Disappointed, Faison left to carry on the plans alone. But the antidote had worked and Helena recovered, although she didn't let anyone else in on her secret. Instead, she plotted to bust up the impending marriage of Nikolas and Katherine. Katherine was pregnant and had trapped Nikolas into marrying her. However, Helena knew the truth: Katherine was sterile as a result of the drugs given to her after the fall from the parapet. On the night of the wedding, Helena put on a blonde wig and pushed Katherine off the parapet she fell from before. Only this time Katherine died as Helena crept back into her sick bed and the police began their investigation. When one of the servants told the police she had seen a blonde woman on the parapet, the cops zeroed in on Laura as their prime suspect. Much to Helena's delight, Stefan confessed to the murder to save Laura. But Stefan began to suspect that his mother was no longer helpless. Since Helena had silenced the only person who could connect her to the murder (Ari), Stefan and Laura cooked up a plan to make Helena believe that Ari was still alive. The plan worked and they caught Helena out of bed trying to use the phone. She was exiled from Wyndemere and became the prime suspect in Katherine's murder, especially when Stefan turned over a tape of the events taken by the ELQ land-sea crane to the DA. To retaliate, Helena tried to tell the cops that Stefan had poisoned her. But there was no evidence to prove this claim. However, her allegations were enough to discredit Stefan in Laura's eyes much to Helena's delight.
Alexis decided to try to gain her chunk of the Cassadine fortune again to help out Jerry Jacks, who was laundering money. As Jax tried to help her find Mikkos' will that would name her as an heir, he found a more important document instead: true DNA results that revealed Nikolas to be Stavros' son and the Cassadine prince/heir. This left Helena back at square one, and she still had to wiggle out of a murder charge. So she decided to frame her partner-in-crime, Faison. She rescued him from jail and then blew up his boat to prevent him from contradicting her. Helena was then free to continue her plans for Lucky Spencer. No one knew that she had him until Stefan discovered him one day at Helena's Nova Scotia retreat although he kept silent about his discovery. Alexis taunted Helena that she also knew that Helena had Lucky. So Helena tried to run Alexis down with her car. However, Helena actually hit Chloe Morgan who was dressed up to look like Alexis. Chloe survived but couldn't remember who was driving the car that hit her.
Helena then sped up her plans for Lucky. She took him on a tour of places important in the history of the Spencers, including Ice Princess Island and his birthplace in Texas. They left clues along the way for Luke and Laura to follow them. Helena and Lucky's last stop was in British Columbia at the Triple L Diner where the Spencer clan had lived before going back to Port Charles. It was there that Helena released Lucky, but it wasn't the same Lucky that she had originally taken prisoner. While in her care, Helena had brainwashed Lucky to focus only on the anger and hatred he felt for his parents when he found out about Luke raping Laura years ago at the Campus Disco. After releasing Lucky, Helena prepared to return to Port Charles, but Stefan intervened by having her arrested for kidnapping Lucky. However, there was no evidence that a kidnapping had even taken place, so she was released. She returned to Port Charles, where she sat back and kept an eye on Lucky while dodging questions from Stefan and Nikolas regarding Lucky's location. When Lucky's doctor talked with Stefan and Alexis, Helena had him killed to prevent any further interaction.
When Lucky returned to Port Charles, he was under Helena's control but didn't realize it for a while. Helena instructed him to push Elizabeth away and encourage her to be with Nikolas, because Nikolas is the one that loves her. This made Elizabeth suspicious and eventually they figured out that he had been brainwashed by Helena, who still had control over him. Lucky then went to a psychiatrist, who tried to deprogram him.
Stefan became a real nuisance to Helena, so she made plans to eliminate him. On board her yacht one night, she poisoned his wine and when the drug took effect, had him tossed overboard to drown. She then turned back to gaining control of the Cassadine fortune and General Hospital, but Alexis countered her every move with a legal move of her own. One night, a drunken Alexis blurted out her opinion that Helena had murdered Stefan.
Helena had also been pursuing Jasper Jacks as a side game. In an attempt to bed him, she bought up the drug company that owned the medication that Jax's beloved Chloe needed. Chloe was suffering from a brain tumor that caused debilitating headaches and scary visions and Jax desperately wanted to help her. So he agreed to Helena's proposition: she would give him the drug and the drug company if he would sleep with her. But much to her surprise, he handcuffed her to the bed instead. Then he made the electronic transaction necessary for him to buy the drug company she had dangled before him. Angry but impressed by Jax's moves, she refused to apologize for her actions. But when Chloe's visions began to reveal how she had killed Stefan, Helena plotted to kill Chloe. She tailed the lovebirds to a tropical island where she disguised herself and attempted to kill Chloe. But Chloe fought her off and Helena escaped undetected. Elsewhere, a very much alive Stefan had plans of his own for Chloe and her visions. He had been hiding out since he had taken precautions against Helena's poison and framed Luke for his demise. Stefan lured Jax away from Chloe by making him think that Brenda Barrett, Jax's old flame, was alive. When Jax went after Brenda, Stefan kidnapped Chloe. When Helena began to grow tired of Nikolas's hatred towards her, she decided to get him declared mentally incompetent and institutionalized. Chloe then had visions of Helena harming Nikolas in some way. She was also losing her eyesight, so Stefan decided to bring them back to Port Charles. Helena was shocked to see her dead son walking onto her yacht just as she was putting into action her mental insanity plans. She recognized in him some of her own cunning. To retaliate against Stefan, Helena informed Chloe that Stefan was behind her kidnapping and Chloe left Stefan.
A few months later, Helena had Lucky poison Lucas with a mysterious virus, and then she approached Lucas' father Dr. Tony Jones with an offer: she would help him cure his son if he helped her to cure her son. Tony was confused until she showed him her underground lab where a cryogenically frozen Stavros was being kept. Reluctantly, Tony agreed to her demands.
When Lucky tried to break free of Helena's control by leaving town with Elizabeth, Helena gave him a ring to give to Elizabeth. Laura recognized the ring as the one she'd been given by Stavros and they realized that Lucky's programming was back. Helena used her power over Lucky to get him to do various things. When Lucky got arrested and thrown in jail for assaulting Stefan, Helena snuck in and gave him the means to start a fire and bust out.
With Tony's help, Stavros finally came back from the dead and Helena was ecstatic. But she was disappointed when his first word was, "Laura!" She had plans for them to destroy their enemies and rule the world, but he wanted to get Laura and Nikolas back to become a family. Helena also wanted Nikolas back in the Cassadine fold. She began to entice him by claiming everything bad he'd heard about his father was a lie. Nikolas wavered at first and Stavros was suspicious of his loyalty. Ultimately, Nikolas became a Cassadine again and even pushed Gia away at Helena's request. But Helena didn't realize that Nikolas and Luke had teamed up to try to find out what Helena's plans were. Stavros told his mother to back off whenever she warned him about wandering around in public and informed her that he wasn't interested in her plans of world domination, just in getting back Nikolas and Laura. He even promised to kill Helena if she tried to come between him and Laura.
Helena enacted the first stage of her plans and summoned Lucky to her lab. Using her powers over him, she commanded him to inject Luke with a biotoxin that would slowly destroy his mind and make him ineffective in trying to stop her. Lucky tried to resist but couldn't and regretfully injected Luke. Helena told Luke that she'd miss him as an opponent before having him dumped in an alley. She later went to see him at his place and in a moment of clarity he nearly strangled her. Helena remained satisfied with Nikolas' behavior and loyalty, but Stavros had his own doubts. To try to gain information about how Helena controlled Lucky, Nikolas ordered her to erase Lucky's memories of Liz so that Nikolas could have her. As Liz secretly watched from her hiding place, Helena used the Ice Princess to systematically erase all of Lucky's memories of love for Liz. After witnessing this, Liz tried several times to find the Ice Princess hidden in Helena's hotel room before she was successful. Helena was not pleased to discover it missing and suspected Elizabeth of stealing it. Elizabeth wasn't certain how to use it and Lucky ended up throwing it into the river. Fed up with Stefan's anger towards her and his plans for the Cassadine fortune, Helena ordered Stavros to get rid of Stefan and frame Jax for the murder. Instead, Stavros killed Chloe when she figured out his identity and Stefan ended up arrested and charged with her murder. As a test of loyalty for Nikolas, Helena forced him to back up her story that Chloe was afraid of Stefan and had come to them for protection. Nikolas complied and passed the test. But Helena continued to doubt his abilities and his choices in women.
Frustrated, Nikolas offered to break it off with Elizabeth. But she had something else in mind: she wanted him to kill Elizabeth. Stavros agreed with Helena's test of loyalty for Nikolas, but warned her that Gia had overheard the request. Helena wondered if Gia would spoil their plans, but was thrilled when Nikolas passed the test and "killed" Elizabeth. When Lucky came by to accuse her of killing Chloe, Luke, and Elizabeth, she produced the Ice Princess that he'd disposed of and got him to admit that Luke was alive but he didn't know where he was located. Stefan had figured out that Stavros was alive and confronted him. Stefan overpowered his brother, tied him up, and demanded that Helena show him her underground lab. When she tried to distract him with praise, he informed her that it was too late for that. Stavros escaped his bonds and went to the lab where Stefan was overpowered and tied up. Then Helena brought Nikolas to the lab to reveal her "secret project." As a last test, Stavros pretended to be still frozen in the chamber as Helena introduced Nikolas to his father. Left alone, Nikolas expressed hatred for Stavros, but kissed the chamber to make it look like he loved Stavros to a spying Helena in the next room. Helena also revealed to Nikolas that she'd programmed Lucky to prevent anyone else from stopping her plans. Helena was elated that Nikolas seemed thrilled by Stavros' return, but Stavros told her what he'd actually said. He told her that Nikolas' hatred hurt him, but roared at Helena to leave Nikolas alone when she suggested that they could program Nikolas to love him.
Putting her plans into full gear, Helena had Alexis and Bobbie brought to her lab and held them hostage with Stefan. Laura and Nikolas went to confront Helena at the lab and found Stavros first. Stavros locked Gia and Nikolas in a room before taking Laura off to the room he'd prepared for her. Jax tried to gain access to the hostages by using Helena's lust for him against her, but Skye interrupted and messed up his plans. Luke then escaped the hospital and went after the captives. He barged into Stavros' room ready to fight, but he was still weak and no match for Stavros. Angry, Stavros told his mother to finish off her plans for everyone. All of the captives were gathered in the lab and Helena revealed her secret weapon: Lucky! But Helena didn't know that Lucky had managed to break through his programming by focusing on his love for Elizabeth. Chaos ensued as the hostages tried to get out while Scott, Roy, and Jax found their way in. Stefan and Lucky tried to stop the menacing computer while Luke ran off after Stavros and Laura ran after Luke. Luke and Stavros fought and Stavros ended up falling into a bottomless pit. Helena nearly escaped before they reached the surface, but she was detained again and arrested once they reached the outside. To ensure Helena's permanent captivity, Stefan cut off her access to money. However, Helena's hopes were raised when Taggert revealed there was little physical evidence to keep her locked up for long. A few months after being captured, Helena feigned illness and was taken to the hospital.
While there, she saw Nikolas and told him a riddle before escaping. She hid out in the stables at Wyndemere where Gia happened upon her. She blackmailed Gia into helping her, and Gia agreed in order to protect Nikolas. But as Luke and the cops searched for Helena, Nikolas grew suspicious of Gia's behavior and confronted her as she was giving money to Helena. Wanting to protect Gia and to get rid of Helena, Nikolas let Helena go. But he warned her never to return under penalty of death. When Luke found out he was horrified and Laura was heartbroken that Nikolas chose to help Gia instead of his family. Luke and Roy set out to track her and experienced a few misses before finding her dressed as a homeless person. Luke grabbed her throat, scaring her, as she tried to entice him with the thrill of the chase. Roy showed up before Luke could kill her and they turned her in to the cops. Luke then accompanied Helena to federal prison and later celebrated her capture. But Luke didn't realize that a Helena look-a-like sat in prison while the real one roamed free. He caught on when he went to see Helena in prison and made a remark that "Helena" didn't counter properly. Luke tracked the real Helena to a convent. Laura followed him and together they sent Helena packing to the Arctic Circle under the guise of missionary work.
Helena wasn't heard from again until Stefan's funeral in October 2003. She returned to dance on the grave of her second son, a disappointment to her, and to hurl insults at all her old enemies. But Luke made her think when he laughed in her face and told her that she's facing a punishment worse than death: she's fading into obscurity.
But Helena returned with a new mission in the spring of 2004 – to destroy Emily and Nicholas. Feeling that Emily wasn't good enough for her grandson, the prince, Helena first warned the couple to break up. When they didn't listen, Helena had Nicholas institutionalized and drugged. Nicholas fought the drugs and found his way back to Emily, who had snuck into the institution to rescue him. With one plan thwarted, Helena found an unlikely ally in Tracy Quartermaine. The two attempted to have Emily jailed for "murdering" Mary Bishop. Lucky Spencer discovered their scheme and announced Helena's plans at Emily and Nicholas' engagement party. Helena, being furious that she had been caught, cursed the couple. It worked, and Emily grew sick as the couple desperately searched for an anti-curse. They found it and were able to cure Emily, but Helena wasn't done yet. Finding Emily alone on the cliff's near Wyndemere, she attempted to stab Emily. Nicholas came to her rescue and wrestled the knife out of his grandmother's hands. Once she dropped the knife and posed no threat (at that exact moment), Nicholas pushed her over a cliff. Helena's body never turned up, leaving everyone in Port Charles to, of course, consider her dead.
Unfortunately, Connor Bishop witnessed Helena's supposed-demise and blackmailed Nikolas. Nikolas soon grew tired of the blackmailing and confessed to the police that he had pushed Helena off the cliffs. He was arrested and sent to jail. In the hopes of luring Helena out of hiding so that Nikolas can be released from prison, Emily was able to convince Connor to pose as Nikolas. She ended up with more trouble than she ever bargained for when Connor raped Emily on the same night that Helena resurfaced. Cornered, Helena tried to shoot Emily but Lucky took the bullet for her instead. In the commotion Helena was able to once again get away. After Lucky recovered from the shooting, Luke devised a plan to once again lure Helena out of hiding. It was a simple and effective plan. Luke transferred $15,000,000.00 of the Cassadine money into Tracy Quartermaine's account on the condition that she return it when Helena surfaced. Helena did come out of hiding and was promptly arrested.
Helena never remains captive for long. Eventually Helena returned to Port Charles when she got wind of the possibility that Nikolas was going to be a father. Despite several paternity tests that revealed Jax to be the father of Courtney’s unborn child, Helena wanted her own test. She kidnapped Courtney and intended to do a DNA test. If Nik was the father of the baby then Helena would raise it. If not the child was not a Cassadine then she would dispose of it. She was never clear how she intended to do that but she was clear that Courtney would not be alive after the child’s birth. Courtney managed to overpower Helena and escape. Helena went into hiding and resurfaced months later when it was revealed that they baby boy Courtney gave birth to was in fact a Cassadine.
Helena hired a nanny who was to help her in the quest to kidnap Spencer but the nanny proved uncooperative when she fancied herself in love with Nikolas. Helena failed to do her homework because it turned out that the nanny had a history of falling in love with the fathers of her young charges and then murdering them when they did not return her affection. In the end it was Colleen who kidnapped Spencer in a desperate attempt to have Nikolas.
When the dust settled, Colleen was dead and Helena managed to snatch Spencer. She would not have him for long. Emily and Nikolas soon tracked Helena down and recovered Spencer. Helena managed to get away.
Helena stayed away from Port Charles for a few years but reappeared by taking over the television monitors during a ribbon cutting ceremony at the hospital during which Helena delivered a cryptic message to Nikolas. She wanted Nikolas to secure a painting for her but he did not immediately meet her demands. While Helena waited, she met Rebecca Shaw, a doppelganger of the deceased Emily Quartermaine. Helena offered to scam Nikolas with Rebecca and was disappointed when Rebecca refused. Helena was also introduced to Luke's son Ethan Lovett. She was intrigued by the similarities between Luke and Ethan and she loved hearing that Luke had fathered an illegitimate child during his marriage to Laura. Eventually Nikolas turned over the painting and Helena took off again.
A few months later, Luke was summoned to Greece. He believed Helena had sent for him and he was surprised to find her locked up. Helena explained that Valentin, an illegitimate son Mikos had fathered, was after her. Helena was poisoned and Luke rescued her and took her to General Hospital. During the hospital stay, Helena discovered that Nikolas was having an affair with Elizabeth even though she was engaged to marry Lucky. Helena used the information to black-mail Nikolas into protecting her from Valentin.
After the threat from Valentin was over, Helena returned to town and badgered Nikolas about producing a suitable Cassadine heir until she learned Elizabeth was pregnant with a child fathered either by Nikolas or Lucky. Helena paid off a lab technician to reveal the results of the paternity test to her first. When she learned Lucky was the child's father, she paid the lab technician to name Nikolas as the father instead. Helena was delighted over the idea of a Cassadine raising a Spencer and she planned to teach the child to despise the Spencer family. A second paternity test was run but Helena changed the results of that test as well.
As Elizabeth's pregnancy progressed, Helena continued to stir up problems between Nikolas and Lucky and she antagonized Elizabeth about the role she planned to have in the life of the new Cassadine heir. Around the same time, Tracy Quartermaine picked up on a connection between Helena and the lab technician and insinuated that Helena had altered the test results. Tracy continued to ask questions and make accusations so Helena had her henchmen chloroform and kidnap Tracy. Helena held Tracy in a dungeon and used her as bait to lure Luke, although Luke and Tracy both made it out of Helena's clutches.
Helena continued her attack on Elizabeth after her baby arrived. She made her disappointment over the child's name of Aiden very clear as she lurked around the hospital. Aiden was kidnapped from the hospital and Helena was accused of kidnapping him until the police pursued another lead. Helena blamed Elizabeth for being an incompetent mother and Lucky worked to bring the baby home to his parents. Helena appreciated the irony of Lucky rescuing his own son and turning him over to Nikolas. Almost a year later the truth of Aiden's paternity was revealed and Nikolas berated his grandmother for her interference in changing the paternity results. Nikolas took his son Spencer and left town.
Helena left after Nikolas but she dropped in again to watch the Spencer family self-destruct when the lives of Luke, Lulu, and Lucky seemed to be in disarray without any interference on her part. Helena also lurked in the tunnels at Wyndemere and spied on Ethan's interactions with a woman named Cassandra. Cassandra was staying at Wyndemere and under Helena's orders posed as a psychiatric patient that suffered from amnesia. Helena planned to have her seduce Lucky but since he left town, she decided that Ethan would be seduced instead. Helena wanted the woman to kill Ethan in front of Luke so he would experience the pain Helena had suffered after Luke had killed her beloved Stavros.
Cassandra's real name was Irena and she was Helena's daughter. Helena was concerned that Irena had developed real feelings for Ethan so she declared the game over and ordered Irena to shoot Ethan in front of Luke. Irena refused to comply so Helena ordered her henchmen to kill Irena instead. She declared her daughter a disappointment but continued to threaten the lives of both Luke and Ethan until Ethan's mother Holly Sutton arrived. Holly claimed that Ethan was not Luke's son. Helena took a hair from both Luke and Ethan and disappeared to run her own DNA test.
Luke tracked Helena down aboard the Haunted Star about a year later and accused Helena of kidnapping Lulu. Helena placed all blame related to the tragedies her family had suffered on Laura and threatened to kill her. While Luke and Laura searched for Lulu aboard the Haunted Star they happened upon Ethan. Helena had kidnapped him as a distraction for Luke when Lucky was unavailable. Helena ordered Laura's death but changed her mind and instead announced that it would be fitting for Laura to murder Luke's son. Helena declared that her curse would be broken with Ethan's death and that his death was the only way to save Lulu. However, Luke, Laura, Ethan, and Lulu's husband Dante turned the tables on Helena and shot her. She died without revealing any information regarding Lulu's whereabouts.
After Helena's death, it was revealed that she had been secretly nursing Stavros back to health on Cassadine Island. A few months prior to Lulu's disappearance, Nikolas paid Helena a visit and discovered that Stavros was alive. Helena admitted that she had changed the paternity results of Elizabeth Webber's son in hopes that the news of a new Cassadine heir would speed her son's recovery. However, Stavros found his own motivation through his obsession with Lulu.
Upon Helena's death, Stavros recovered her body and took her back to Cassadine Island. He provided his mother with the same cryogenic treatment that she had given him after his presumed death. Even after Helena's death, she continued her revenge against the Spencer family. When Luke was diagnosed with Polonium 210 poisoning, a courier delivered a posthumous message in which Helena revealed that she was responsible for his current health crisis. Even in death, Helena continued her game with Luke and bragged that he would die at her hands unless he found the cure which was not located in Port Charles. As Luke's illness progressed, he experienced a vision of Helena in which she offered to kill him in order to spare him from the slow death of Polonium poisoning.