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 Cast
 Tobey Maguire as Peter Parker / Spider-Man:
A photographer for the Daily Bugle who leads a double life as the superhero Spider-Man, protecting New York City from crime.
 Kirsten Dunst as Mary Jane Watson:
Peter Parker's love interest and a Broadway actress.
 James Franco as Harry Osborn / New Goblin:
The son of Norman Osborn and Peter Parker's former best friend who believes that Spider-Man murdered his father. After learning Peter Parker is Spider-Man, Harry becomes the New Goblin to battle his former friend directly.
 Topher Grace as Eddie Brock, Jr. / Venom:
A photographer at the Daily Bugle. He grows increasingly embittered toward Peter Parker, who beats Brock to photography gigs and has attracted the attention of Brock's girl, Gwen Stacy.
 Thomas Haden Church as Flint Marko / The Sandman:
A small-time thug who has a wife and daughter. An accident gives him the ability to change his body into malleable sand, transforming him into Sandman. He is now believed to be the person responsible for Uncle Ben's death.
 Bryce Dallas Howard as Gwen Stacy:
Daughter of a police captain, George Stacy, and a science student of Dr. Curt Connors. She competes with Mary Jane Watson for the love of Peter Parker, her lab partner, despite Eddie Brock, Jr's feelings for her.
 Rosemary Harris as May Parker:
The aunt of Peter Parker and the widow of Ben Parker, Peter's uncle. Peter has not told her of his vigilante role in protecting New York City as Spider-Man.
 Dylan Baker as Dr. Curt Connors:
A college physics professor under whom Peter Parker studied and with whom he has maintained a good friendship.
 J. K. Simmons as J. Jonah Jameson:
The aggressive chief of the Daily Bugle. He carries a personal vendetta against Spider-Man, whom he considers a criminal.
 Daniel Gillies as John Jameson:
The son of J. Jonah Jameson and an astronaut who was left at the wedding altar by Mary Jane Watson. He brings back the symbiote with him to Earth from outer space.
 James Cromwell as Captain George Stacy:
A police captain and father of Gwen Stacy. He shares the news with Peter and May Parker that new evidence indicates that Flint Marko killed Uncle Ben.
 Theresa Russell as Mrs. Marko:
The wife of Flint Marko / Sandman.
Elizabeth Banks as Betty Brant:
The secretary to J. Jonah Jameson at the Daily Bugle.
 Cliff Robertson as Benjamin "Ben" Parker:
The husband to May Parker and uncle of Peter Parker. Killed by a criminal with the primary suspect originally being the carjacker. Spider-Man lives by Ben's words: "With great power comes great responsibility." The police find new evidence that indicates that Flint Marko, not the carjacker, had killed Uncle Ben.
Tim DeZarn as Philip Watson:
The abusive father of Mary Jane Watson.
Michael Papajohn as Carjacker: The criminal who was thought to have killed Peter Parker's Uncle Ben in the first film, though new evidence suggests someone else murdered Ben Parker.
Willem Dafoe as Norman Osborn / Green Goblin:
The deceased father of Harry Osborn who appears to his son in hallucinations.
Stan Lee has a cameo in Spider-Man 3, as he did in the previous Spider-Man films. Unlike his previous Spider-Man cameos, he has dialogue with Peter Parker in his cameo for this film. Lee has referred to it as his "best cameo" in an interview. Bruce Campbell, who has had cameo roles as a wrestling ring announcer in Spider-Man and as a rude usher in Spider-Man 2, returns in Spider-Man 3 with a new cameo. Sam Raimi has a cameo in Spider-Man 3 as a Navy admiral.
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