Dr. Curt Connors, Peter's one-armed teacher in the film, is the man who will later become The Lizard, one of Spider-Man's longest running enemies.

In the scene where J. Jonah Jameson is thinking of a name for Octavius, Hoffman shouts out "Dr. Strange" and JJJ says "Already taken." Dr. Strange is another Marvel hero who lives in New York.

The shot where Peter dumps the Spider-Man costume in the trash and walks away is a direct copy of a frame from the comic issue entitled "Spider-Man No More." This page was pencilled by one of the longest running creator's of Spider-Man John Romita Snr.

When Peter hits the ground after failing to clear the building, he gets up and complains about his back hurting. Tobey Maguire (Peter) almost didn't reprise his role as Spider-Man because of a back problem.

"The Punisher" has a small cameo in Spider-Man 2. At the end when Mary Jane is running through the park with her wedding dress on, Thomas Jane can be seen glancing at her while she runs past. [This cameo has been highly debated for the fact that Jane is not credited. While uncredited cameos are not unusual, there does not appear to be any reliable source that confirms or denies his cameo in the film.]

The annoying usher that doesn't let Peter into the theater to see Mary Jane's play is none other than Bruce Campbell, who makes a cameo/stars in most of Sam Raimi's movies. He was also the ring announcer in the first movie.

John Jameson later becomes The Man-Wolf in the comics.

In the hospital scene when Doc Ock's mechanical arms are attacking the surgeons, there is a scene where the camera cuts to a surgeon raising the chainsaw in the air. That scene looks a lot like the scene from "Evil Dead 2" (1993) where the camera does the same thing when Ash grabs the chainsaw to cut off his hand. Another Sam Raimi film.

Peter's landlord is Mr. Ditkovitch. Steve Ditko was the co-creator of Spider-man.

Spider-Man creator Stan Lee makes his standard cameo appearance for this film when Spider-Man and Doc Ock are fighting on the side of the building. The first shot of the street during the fight shows a woman being pushed out of the way as some debris falls; the man pushing her is Lee.

In the scene where Peter drops his books on the college grounds and bends down to pick them up, a black bag comes by and smacks Peter in the face. The person carrying the bag is director Sam Raimi.

In one scene after Spider-Man has lost his powers, he catches a ride on an elevator. On one floor, a young man gets on and comments about Peter's "great Spidey costume". Peter says he made it himself, it itches, and rides up in the crotch, causing a strange look from the young man. The young man was Hal Sparks, who plays Michael Novotny on the US version of "Queer As Folk". Michael's a gay comic book store owner and diehard fan (and walking encyclopedia) of the whole superhero genre.

When Spider-Man sets the pizzas on the balcony, we see a man try to steal a piece. This man is Scott Spiegel. Spiegel has appeared in almost all of Sam Raimi's films, including The Evil Dead, Darkman, and the first Spider-Man.

The two boys on the train that return the mask to Peter are in fact Tobey Maguire's (Peter Parker/Spider-Man) half-brothers.

Sam Raimi brings his trademark Oldsmobile (which appears in all his films bar "The Quick and the Dead", for obvious reasons) back for Spidey 2. It makes a number of guest appearances at Aunt May's house.

In the scene right after Doc Ock's foiled bank robbery, where he, Spidey, and Aunt May climb around on the building side, the actors - including 76 year old Rosemary Harris - actually were hanging from the building, secured by wires.