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Skull size variation in the orange mouse opossum Marmosa xerophila Handley and Gordon, 1979 in Venezuela was analysed by sex and geographic location. Morphometric relationships between the species and the closely related M. robinsoni Bangs, 1898 were also studied. Results showed that M. xerophila is a sexually dimorphic and geographically homogeneous species. Males had larger skulls than females although dimorphism was mainly related to length, height, and some dental parameters. Interspecific comparisons revealed that M. xerophila has a smaller skull than M. robinsoni, even in the sympatric area where the smallest specimens of M. robinsoni occur. Discriminant function analyses between these species, for males and females separately, provided accurate classification functions that allowed correct specific determination. In Venezuela, M. xerophila lives in arid lands with xerophilous thorny woodland and scrub, up to 90 m above see level.