During the late Pleistocene, a large number of species colonized North America from Eurasia through the Bering Land Bridge. At least four different genera within the tribe Ovibovini are known from this time, the holarctically distributed Ovibos moschatus (the extant musk ox) and Praeovibos, and the nearctically distributed Bootherium and Euceratherium. Questions about the taxonomic relationships of the four North American musk oxen arose soon after their description and continue to be unresolved at the present. In this study we present the first DNA and protein analyses, of the four mentioned genera. Phylogenetic analysis at the mitochondrial level indicates that Praeovibos falls within the diversity of modern Ovibos, which might indicate that Praeovibos is simply an earlier morphotype of the extant species O. moschatus. In contrast Euceratherium and Bootherium are clearly distinct genera, in agreement with the findings of previous morphological studies.