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You don't have to beat the Pokemon League more than once to be able to get Mewtwo. First, you must be sure that you have the National Pokedex (the Pokedex where you have all the numbers of Pokemon on it). Second, make sure that you have defeated the Pokemon League at least once. Then, after defeating the Pokemon League at least once, the cave in Cerulean City will be open, and the man guarding the cave will no longer be in front of the entrance. In that cave lies Mewtwo.

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