The basis of the "What If?" series is to give Marvel fans a glimpse into the road less travelled by their favorite and not-so-favorite heroes with mild to moderate success. It's also worth noting that, ninety percent of the time, "What If?" stories don't have a happy ending.
In normal Marvel continuity (Earth-616 as it is sometimes called), Spider-Man once gained four extra arms due to an untested antidote to his spider-powers. Later on, he managed to get rid of these thanks to a sample of Morbius' blood and the efforts of Doctor Curt Connors. This issue focuses, however, on the question: What If Spider-Man Had Kept His Six Arms?
The book opens with Uatu the Watcher telling us the events of Earth-616 leading up to the first appearance of Morbius. In normal Marvel continuity, the Living Vampire made it to Spider-Man's laboratory in Doctor Connor's Long Island home, but in this reality, Morbius was set upon by sharks after leaving the boat he was travelling on, never reaching land and encountering Spider- Man. As scraps of Morbius' costume wash ashore, we see the Web-Slinger bemoaning the fact that it looks like he'll have to keep his six arms.
Spider-Man returns to the laboratory and finds a ready and willing Doc Connors to assist him. The two work through through the days and nights, but inevitably, Doc Connors succumbs to the stress and transforms into the Lizard! The two slug it out, destroying all of their research in the process, but the duel is over quickly due to Spider-Man's extra arms. Spidey then whips up an antidote for the Lizard, who changes back to Doc Connors. Spider-Man tells Connors that the doctor should go home, and Connors agrees but suggests that Spider-Man go see Professor Charles Xavier, who may be able to help.
Some time later, Spider-Man reaches the Xavier Mansion. He comments that the extra arms are handy, but hopes that Professor Xavier can help him leave without them. Suddenly, the Beast tackles Spider-Man! The mutant didn't recognize Spider-Man because of the extra arms, and soon Cyclops, Iceman, and Angel attack as well. Angel captures Spider-Man, who quickly escapes his grasp. However, the brawl is halted by the arrival Marvel Girl (Jean Grey) and Professor Xavier. Xavier knows why the Web-Slinger has come to the Mansion, and a short time later, the pair are in another laboratory. The results of Xavier's test show that the extra arm mutation has become irreversible, and Spider-Man snaps at him. After Spider-Man apologizes, Xavier attempts to cheer him up, but fails.
Spider-Man leaves the X-Mansion, and thinks about how his mutation is going to affect those he loves, especially Aunt May. The consquences of his mutation weighing on his mind, he makes his way to the Baxter Building to speak with Reed Richards, who reaches the same conclusion about Spider-Man's mutation: it's irreversible. Ben Grimm comes in, and Spider-Man assumes that the Thing is there to preach to him. Wanting none of it, Spidey attacks, and the two spar until Reed pulls them apart. Spider-Man apologizes, and Ben tells Spidey why he came: Doctor Octopus is holding hostages at city hall, and is demanding that Spider-Man show up.
Knowing that with great power comes great responsibility, Spider-Man goes off to face Doctor Octopus, despite his "handicap". He arrives at the last moment, and as Doc Ock lunges to attack, Spidey reveals his six arms. Doctor Octopus is taken off guard, and Spider-Man makes short work of him because of it. Meanwhile, another foe of Spider-Man is watching the events with malicous glee: J. Jonah Jameson. The esteemed publisher plots to use Spider-Man's arms to make the public hate him, but is discouraged by Robbie Robertson.
Over the next few months, Spider-Man becomes a superhero nearly full-time, avoiding friends and family because of his bizarre mutation. However, Mister Fantastic has a surprise for Spider-Man, and he presents the the web-slinger with four electro-vibra arms that will render Spidey's extra appendages invisible. Utilizing the arms, he manages to live a normal life once again. When Aunt May dies later of natural causes, however, Spider-Man is prepared to once again become a full-time crime fighter. During his career, Spider-Man's extra arms allow him to become an even more skilled hero, defeating the likes of Thanos and Mephisto, along with his usual rogue's gallery including new- comer Venom. Also, Spider-Man manages to save Gwen Stacy from the Green Goblin.
In conclusion, Spider-Man becomes a spokesman for the physically challenged, and inspires all to rise to their true potential.