Richard Damien, a wealthy businessman and avid collector hires Shikata, swordswoman, to capture Spider-Man for his collection of rare animals. Shikata and Spider-Man soon have their first head-to-head fight and Shikata decides that he is too noble a foe to simply capture - they must fight to the death. Shikata informs Richard Damien that they no longer have a deal and that instead she plans to lure Spider-Man into the fight of his life. Richard is not a fan of this alternative strategy and sends his thugs to kill Shikata. Unfortunately, it is the goons who find themselves victims of Shikata instead. Afterwards, Shikata hunts down Spider-Man and informs him that they must fight until one of them is dead. Soon the pair is engaged in an all out brawl on the streets. Things begin to look grim for Spider-Man until Mary-Jane Watson arrives on the scene with a bit of information that may help Spider-Man vanquish Shikata without compromising his integrity.

Peter Parker earns much needed cash by working at the lab for his professor, Doc Connors, a world class scientist. Doc Connors is studying reptilian DNA for its regenerative powers. This is extremely important to Doc Connors because he lost an arm in an industrial accident at Oscorp years before. Meanwhile, as the year anniversary of the death of Norman Osborn approaches, Harry Osborn reluctantly asks Peter and Mary-Jane Watson for help sorting through his father's personal effects. Back at the lab, Doc Connors secretively injects himself with reptilian DNA that not only stimulates his arm stump to grow again but also has the undesired effect of slowly changing Doc Connors into an angry, vengeful Lizard. As the serum effects the Doc's brain, he begins seeking revenge on those who have harmed him and next on his list is Harry unless Spider-Man is able to stop his beloved professor in time.