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In order to battle Mewtwo, you first need to get all 10 trophies in the Stadium Mode as well as the Gym Leader Castle.
Once you have done that, the VS Mewtwo bonus tournament will open up on the map. To access it, simply move your Magne-cursor up to the top. Unlike the other battles in the Stadium and Gym cups, the VS Mewtwo tournament allows you to enter six Pokémon.
Mewtwo knows Psychic, Blizzard, Thunderbolt, and Rest, three damaging moves and one recovery move. Bring along Bug, or Ghost Types to get the advantage. Or you can use a Ditto to transform into Mewtwo and then battle.