The echimyid rodents of the genus Thrichomys vary considerably in their behavior and feeding ecology, reflecting their occurrence in environments as different as the Caatinga, Cerrado, Pantanal, and Chaco biomes. While the genus was originally classified as monospecific, a number of Thrichomys species have been recognized in recent decades, based on morphometric, cytogenetic, and molecular analyses. While Thrichomys is well studied, the variation found in its cranial morphology is poorly understood, given the taxonomic and ecological complexities of the genus. Using a geometric morphometric approach, we characterized the differences found in the cranial morphology of four Thrichomys taxonomic units, including three established species, Thrichomys apereoides, Thrichomys fosteri, and Thrichomys laurentius, and one operational taxonomic unit (OTU), Thrichomys aff. laurentius. No significant differences were found among these units in cranium size, but significant variation was found in skull shape. The Procrustes distances provided a quantification of the differences in the shape of the skull, with the largest distances being found between T. aff. laurentius and T. fosteri in the dorsal view, and between T. aff. laurentius and T. apereoides in the ventral view. A Discriminant Function Analysis (DFA) with cross-validation determined that the pairings with the highest correct classification were T. aff. laurentius vs. T. apereoides and T. aff. laurentius vs. T. fosteri, in both views. The principal variation in skull shape was found in the posterior region and the zygomatic arch, which may be related to differences in diet.