High school student Peter Parker (Andrew Garfield) is haunted by the disappearance of his parents (Campbell Scott, Embeth Davidtz).
He lives with his uncle Ben (Martin Sheen) and aunt May (Sally Field) and contends with all the usual growing pains, including persistent bullying from jock classmate Flash Thompson (Chris Zylka).
A tender romance with fellow student Gwen Stacy (Emma Stone), daughter of police chief Captain Stacy (Denis Leary), keeps Peter on an even keel until he is bitten by a genetically modified arachnid that imbues him with superhuman powers.
At the same time, Peter discovers evidence linking his parents’ disappearance to his father’s business partner, Dr Curt Connors (Rhys Ifans).
Little does Peter realise that Connors also has a secret alter ego: reptilian menace The Lizard.
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