The origin of the genus Bos is a debated issue. From 0.5 Ma until historic times, the genus is well known in the Eurasian large mammal assemblages, where it is represented by Bos primigenius. This species has a highly derived cranial anatomy that shows important morphological differences from other Plio-Pleistocene Eurasian genera of the tribe Bovini such as Leptobos, Bison, Proamphibos-Hemibos, and Bubalus. The oldest clear evidence of Bos is the skull fragment ASB-198-1 from the middle Pleistocene (0.6–0.8 Ma) site of Asbole (Lower Awash Valley, Ethiopia). The first appearance of Bos in Europe is at the site of Venosa-Notarchirico, Italy (0.5–0 .6 Ma). Although the origin of Bos has traditionally been connected with Leptobos and Bison, after a detailed anatomical and morphometric study we propose here a different origin, connecting the middle Pleistocene Eurasian forms of B. primigenius with the African Late Pliocene and early Pleistocene large size member of the tribe Bovini Pelorovis sensu stricto. The dispersal of the Bos lineage in Western Europe during middle Pleistocene times seems to coincide with the arrival of the Acheulean tool technology in this continent.