American teacher Frank Tupelo (Johnny Depp) is on a train travelling from France to Italy when he is approached by beguiling stranger Elise Clifton-Ward (Angelina Jolie). The pair spend the journey exchanging flirtatious banter, and, despite niggling suspicions that Elise is not what she seems, he agrees to stay with her in Venice.
After spending the night together, however, Frank receives a rude awakening when Elise's hotel room is stormed by gunmen. Narrowly dodging death, the seemingly marked man is arrested, unaware that the mysterious new lady in his life has ensnared him in a terrible trap. Elise's ex-lover Alexander Pierce has stolen millions of dollars, and unlucky lookalike Frank is the unwitting victim of an intricate set-up.