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Cerradomys is a monophyletic genus that includes four known species, Cerradomys subflavus, C. maracajuensis, C. marinhus, and C. scotti, distributed throughout the open vegetation belt across South America, from northeastern Brazil to southeastern Bolivia, and from eastern to northwestern Paraguay. We revised the status of the species currently assigned to this genus by analyzing skins, skulls, karyotypes, and cytochrome b DNA sequences. We also described two novel species, one distributed in the Brazilian states of Minas Gerais, Bahia, and Sergipe, and the other in the states of Paraíba, Pernambuco, Piauí, Ceará, and Maranhão. Molecular analysis suggested the following phylogenetics arrangement: (((C. subflavus–C. sp.n.2) C. sp.n.1) C. scotti)(C. marinhus–C. maracajuensis)). Apparently, both novel species inhabit the Caatinga domain and penetrated the coastal Atlantic rainforest, differing from the remaining congeneric species that are typical open-area inhabitants.