Kaine was the first of the Jackal's experiments in cloning that did not immediately degenerate into raw genetic waste. He was a clone of Peter Parker, the original Spider-Man. After some time, however, slow genetic deterioration became apparent. The Jackal became disgusted by yet another failure and planned to kill his creation, forcing the rejected clone to flee. The clone came to call himself Kaine and eventually adopted a costume that slowed his deterioration and hid his skin, but reproduced the web-like scars that run all over his body. Even as his DNA deteriorated, Kaine grew taller and stronger than the original Spider-Man.
Unable to live a normal life because of his disfigured features, Kaine's anger grew with his strength. Most of all he hated Scarlet Spider whom he, like the Jackal, believed to be the original Spider-Man, and thus the reason for his tormented existence. Believing Peter to be a successful clone, Kaine took it upon himself to ensure that Peter led the charmed life denied the Jackal's other experiments. This ambition eventually led Kaine to murder the Grim Hunter and Dr. Octopus (Otto Octavius).
Kaine followed Ben around the world, working occasionally as a high-priced assassin. In Salt Lake City, three years after leaving New York, Kaine killed Detective Louise Kennedy, the only person who ever made Kaine feel loved, after learning that she was in league with the local mob. Ben was spotted at the scene shortly after, and Kennedy's partner, Detective Jacob Raven, eventually tracked Reilly's fingerprints back to the original Peter Parker in New York City and arrested Peter. Peter was exonerated only after he threatened to make his secret identity known and Kaine confessed to the crime in another effort to preserve Peter's happiness. After Ben was "revealed" to be the original Spider-Man, Kaine escaped from police custody but was killed by Spidercide, a shape-shifting clone of Spider-Man. The Jackal put Kaine's body in a clone regeneration pod, where it was revived some time later.
Still attempting to crush Reilly's spirit, Kaine used Elizabeth Tyne (who was living under the assumed name of Janine Godbe after shooting her abusive father), the love of Ben's life since they had met in Salt Lake City. Threatening to expose her to the police, Kaine ordered Janine to fake her own suicide and leave Ben as he wandered America. After Ben took the role of Spider-Man, Kaine lured Janine back to New York and attempted to kill himself and them. Their love inspired him to relent, and both Kaine and Janine surrendered to the police.
Kaine later escaped from prison and was last seen in Greece until he reappeared tracking Raptor; an associate of Ben Reilly's, who believed Reilly to have killed his family. When Raptor mistakenly approached Peter Parker concerning his family's deaths, Kaine ultimately stepped in and killed him.
Kaine was later hunted down by the Kravinoff family in their quest to kill all the "Spiders," hoping to resurrect Kraven. Peter's blood was needed to perform the ritual, however, Kaine knocked Peter unconscious, posed as him, was killed, and his sacrifice was used to bring Kraven the Hunter back to life. Yet, the resurrection could only be successful with the true blood of Peter Parker, and as a consequence Kraven is undead rather than truly alive.
Though it seemed Kaine had in death found the peace he'd never known in life, it was short-lived. He emerged from his grave, regenerated, alive, and mutated. This coincided with the reappearance of the Jackal, who informed Kaine that his cells will always regenerate and that he was to be the first subject in his grand experiment. The Jackal transformed Kaine into a hulking man-like spider whom he named "Tarantula". Under the control The Queen, Tarantula acted as The Jackal's henchman and was sent to contaminate the cure for the Spider-Island virus at Horizon Labs. While there, he encountered Spider-Man who battled him to a standstill. Tarantula quickly blinded Spider-Man with his webs and dangled him over the giant pool of cure, only to have him regain his Spider Sense at the last possible instant. In one swift move, Tarantula was thrown into the pool. As Spider-Man looked on, Kaine emerged from the pool, freed of The Queen's mind control, the Jackal's mutation, and his own degeneration scars. He then informed Spider-Man that The Queen was behind Spider-Island.