By this time, Peter has had his powers for approximately six months. His aunt is still trying to get him with Mary Jane. Peter still needs an alibi. Recently, Peter hasn't been feeling well. First he's climbing a wall, then he loses grip due to temporary lack of spider powers. He finally falls to the ground right after his powers come back and his spider endurance saves him.
One day, Gwen invites Peter to a fashion show hosted by Roderick Kingsley (Christopher Plumber) and financed by Wilson Fisk. They pay some thug to look like some nice admission guy. Peter says that he doesn't like fashion very much to Gwen, but she doesn't take that as an insult because she knows that boys don't like fashion as much as girls and he is there for her and she also knows Peter's photographic occupation. Simultaneously, Kingsley is contacting the Kingpin through webcam and saying that "everything is going to plan" and that they have enough money to rob Norman Osborn's super-soldier serum. In the comics, Roderick Kingsley has another alias.
Later that night, Peter is walking home from the fashion show. His spider-sense tells him some pedestrian (James Roday) is following him. He's never seen him before nor does his spider-sense tell him the pedestrian's purpose of following him. He goes home and the pedestrian walks away.
The next morning jolly ol' Jonah accepts Peter's photos without persuasion from Robbie for once. The pedestrian comes into the Bugle and JJJ has to talk to him privately in his office. His name is revealed to be Mac Gargan and he tells Jameson that he just cannot find how Peter gets photos of, well, himself (but they don't know that). But Jonah has another assignment. He found out that a man named Farley Stilwell can cause artificial mutations and he thinks that will help him destroy Spider-Man. In the lab, Dr. Stilwell decides to give Gargan a scorpion-based mutation because scorpions are the natural predator of spiders. He thus has to don a costume with a tail and is given the proportionate abilities of a scorpion. He is dubbed Scorpion and looks for Spider-Man. After he finds him, he knocks him out cold with just a few punches. Later, Scorpion undergoes a permanent mutation, taking his ability to distinguish right from wrong away. He is eventually arrested for terrorizing the streets.
After Peter wakes up, his thighs hurt bad. He decides to go to Dr. Connors (Rhys Ifans) and get help. Connors says that his powers are a consequence of neogenics in his blood. He says that Spider-Man will either gain more spider-like abilities or lose his abilities all together.
Later that night, Aunt May is paying Bingo at Mrs. Watson's house. Peter is so sick, he doesn't even feel like wearing anything on his torso anymore. His thighs hurt bad. He grows four extra arms. He cuts holes in his costume and goes to get help from Professor Charles Xavier (Patrick Stewart). When entering the school, Wolverine (Hugh Jackman), Cyclops (James Marsden) and Storm (Halle Berry) go after him because they think he is an anti-mutant. Beast (Kesely Grammer) takes a more logical approach asking which two people he (Spider-Man) is with and why he is at the school. Spider-Man explains that he is with nobody and he has simply grown six arms and he is there to speak with Professor X. After he explains that he wants his four arms to disappear, Prof. X refuses and says that if he wants to join the school, he may.
Spider-Man leaves the school and goes to the Baxter Building to ask the FF what to do. Thing (Michael Chiklis) and Human Torch (Chris Evans) suggests that either of them destroy his extra arms. Invisible Woman (Jessica Alba) says that her husband, Mr. Fantastic (Ioan Gruffudd) can help. And he did help enough. He made it to where Spider-Man's arms disappear and can go through anything when he wants them to.
At Osborn's manor, Norman is thinking what it would be like to know the formula of the super-soldier serum that created Captain America. He thought only one with a photographic memory could remember what the serum was. He makes his final edit on the serum and tests it on himself. He gets knocked out cold in his lab letting Roderick Kingsley get in. He steals the serum to get it back to Kingpin. Kingpin's scientist edit it and inject it into Roderick Kingsley. He becomes the Hobgoblin. After Norman wakes up, he becomes the Greengoblin. Both goblins make gliders and bombs. Both run into each other when looking for Spider-Man. They devise a plan.
They invade Oscorp (well, Hobgoblin invades Oscorp because it's Greengoblin's property. Then again, Greengoblin gave Hobgoblin permission so neither are invading Oscorp). Peter notices it and he decides to help because he knows that Harry's dad is in there. So he gets his holed costume on and goes in there with six arms. He goes against Hobgoblin first. His enhanced abilities help him to successfully web him up. He goes after Greengoblin afterwards. He (Spider-Man) asks "Why are you invading Mr. Osborn's property?" Greengoblin replies "How are you so sure I'm actually invading it?" Spider-Man doesn't answer and instead fights. Greengoblin flies out of the building and snatches Gwen who was there with Harry. He takes her to the Brooklyn Bridge. After some retorts from Spider-Man, he pushes Gwen off the bridge and dies, despite Spider-Man trying to help her. He gets Greengoblin down, unmasks him and knocks him out. After he wakes up, he has no memory of being the Greengoblin. He says "Wha- Why am I on the Brooklyn Bridge? Wy am I in this ridiculous costume? I have to get back to the lab to edit more of my serum." Spider-Man says "Mr. Osborn, all that glitters is not gold. Nobody remembers the formula. There's no use trying." Spider-Man then brings him home. Spider-Man goes to Curt again to see if he knows the cure for his extra arms. Curt uses the neogenic recombinator on Spider-Man and his arms disappear permanently.
At home, Peter sews his costume before realizing he has a spare. His aunt comes home and he sees MJ for the first time in this continuity. She says the same thing she says in the comics: "Face it, tiger. You've hit the jackpot!"