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Emanuel Ramirez as Peter Parker / Spider-Man: A social outcast whose parents died early in his life. As a high school student, he is bitten by a radioactive spider and gains spider-like abilities.[2]
Emma Stone as Gwen Stacy: A high school classmate and love interest of Peter Parker.[3]
Rhys Ifans as Dr. Curt Connors / The Lizard: A scientist who tests lizard serum on himself in an attempt to regain his missing right arm, which unexpectedly transforms him into a reptilian humanoid monster.[4][5] In a September, 2011 interview, Ifans claimed that his character spends the majority of the film as a human. While filming for the 9-foot tall Lizard, Ifans was required to wear a CGI suit. Initially, a large stunt-double was used as a stand-in for the role but Ifans insisted on portraying the transformed character, to which Webb agreed. Commenting on the technology used to bring his character to life, Ifans continued "I had a green suit on, and then this cardboard head, and these big claws… Each and every time you see the Lizard, the technology is so advanced now that when the Lizard's eyes move, they're my eyes. If I frown or show any emotion, they're my emotions. That's how spectacularly advanced technology is."[6]
Martin Sheen as Ben Parker: Peter Parker's uncle.[7]
Sally Field as May Parker: Ben Parker's wife, and Peter Parker's aunt.[8][9]
Denis Leary as Captain George Stacy: Gwen's father and a New York City Police Department captain.[10]
Chris Zylka as Flash Thompson: Peter Parker's high school nemesis, a football player who constantly bullies Peter while simultaneously idolizing his alter ego, Spider-Man.[11]
Irrfan Khan as Nels Van Adder
Annie Parisse as Van Adder's wife.[12]
Campbell Scott as Richard Parker: Peter Parker's father.[12]
Embeth Davidtz as Mary Parker: Peter Parker's mother.[12][13] Davidtz replaced Julianne Nicholson in the role.
C. Thomas Howell as Ray: A construction worker whose son is saved by Spider-Man.[14]
Hannah Marks as Missy Kallenback: An unpopular girl who has a crush on Peter Parker.[15]
Miles Elliot as Billy Connors: Dr. Curt Connors' son.[5]
Spider-Man co-creator Stan Lee has a cameo, as he did in the previous films, which will involve him in an action scene and which he referred to as his "best, most unusual one yet!"[16] At the 2011 Dallas Comic-Con, Lee enthusiastically talked about his cameo. He will play a librarian listening to music on his headphones while stamping books and dancing at the same time, despite the on-going fight between Spider-Man and The Lizard.[17]