The cranial anatomy of the Deseadan species Medistylus dorsatus (Ameghino, 1903) is described based on new and complete material from Cabeza Blanca (Chubut, Argentina). Medistylus is the largest of the Pachyrukhinae and the specimen described here is probably the best-preserved pachyrukhine skull known in the Paleogene of South America. Previously, the validity of the species and its phylogenetic affinities with Interatheriidae (Notoungulata, Typotheria) were ambiguous and not conclusive. The syntypes, now reported lost, were isolated teeth poorly described by Ameghino in 1903. This almost complete skull with teeth provides more diagnostic features in order to complete the knowledge of genus. Details about cranial and dental morphology allow the reassessment of Medistylus dorsatus and its inclusion within the subfamily Pachyrukhinae (Hegetotheriidae, Notoungulata). Its cranial and dental specializations and the apparent sympatry with its close relatives Prosotherium garzoniAmeghino, 1897 and Propachyrucos smithwoodwardiAmeghino, 1897 all imply a narrow niche partitioning among the Pachyrukhinae during the Deseadan (late Oligocene). The occurrence of three euhypsodont genera of Pachyrukhinae in the Deseadan of Patagonia reflects the major radiation of the rodentlike ungulates in the Cenozoic of South America and suggests a great paleoenvironmental difference between the late Oligocene faunas of Patagonia and those from Bolivia and Uruguay, where they did not live.