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In the game Pokémon FireRed & LeafGreen, Mewtwo can be encountered in the Cerulean Cave after players complete the Sevii Island's quest that involves the delivery of the key item Sapphire to Celio.
The Sevee Island quest can only be done after the player defeats the Elite Four, and obtains the National Dex
(which involves having 60 species registered in the Kanto Dex).
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