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Frank (Depp) is an American tourist visiting Italy to mend a broken heart. Elise (Jolie) is an extraordinary woman who deliberately crosses his path in order to mislead all those following her former lover, Alexander Pearce, a criminal wanted in fourteen countries who has stolen money from a gangster (Berkoff) and is being pursued by an agent (Bettany). Against the breathtaking backdrop of Venice, Frank attempts to forge a potential romance but soon finds himself a target as he and Elise are caught in a whirlwind of intrigue and danger.
The movie follows the series of manipulations, as characters realise that they are merely pieces being played by an unseen mastermind of the game.