A case of vaginal xanthoma in a 3-year-old Holstein cow is described on the basis of macroscopic, microscopic and immunohistochemical findings. A pink-colored mass surgically excised from the vagina was hard, nodular and 328g in weight. Histopathologically, the mass was consisted of lobular areas surrounded by a stroma and composed of numerous foamy macrophages, abundant lipid material, rarely giant cells and cholesterol clefts. Immunohistochemically, the mass was positive for vimentin, proliferating cell nuclear antigen (PCNA) and CD 68, but negative for smooth muscle actin (SMA), glial fibriler acidic protein (GFAP) and S100 protein antibodies. To the authors' knowledge, this is the first report of a vaginal xanthoma in a cow.