Ten equine skin tumors that had been classified as schwannomas on routine histological examination were analyzed by polymerase chain reaction for bovine papillomavirus DNA. All 10 were positive for bovine papillomavirus 1 or 2, and all 10 were immunohistochemically negative for S-100 protein and strongly positive for vimentin. Nine tumors were moderately positive for laminin and 8, for smooth muscle actin. Five tumors were variably and weakly positive for type IV collagen. The lack of S-100 protein expression made Schwann cells an unlikely cell of origin, as opposed to peripheral nerve sheath tumors, which typically express S-100 protein, at least in some neoplastic cells. The immunohistochemical reactivity is consistent with myofibroblastic origin of the neoplastic cells, although smooth muscle cell or pericyte origin cannot be ruled out. These tumors represent an atypical form of equine sarcoid. Polymerase chain reaction for bovine papillomavirus and S-100 immunohistochemistry are strongly recommended for all equine skin tumors with histological characteristics typical of schwannoma or peripheral nerve sheath tumor.