Megaoryzomys curioi is a thomasomyine, not an oryzomyine as previously believed. This rodent was originally described, from three bony fragments found in a cave on Isla Santa Cruz, Galápagos, as a new species of the Antillean oryzomyine genus Megalomys. The genus Megaoryzomys was named recently for this species, based on new material from Isla Santa Cruz. Our study of additional material indicates that Megaoryzomys curioi is not closely related to Oryzomys but is most similar to large species of Thomasomys, a genus confined to mainland South America. The Galápagos have been colonized by cricetine rodents at least three times, once by a thomasomyine and twice by oryzomyines. Of these colonists, Megaoryzomys curioi is the most divergent from mainland relatives and thus is probably derived from the earliest immigrant. Although the time of extinction of Megaoryzomys curioi has not been determined, and it has never been recorded from life, it probably survived into historic time.