Two cases of either peripheral odontogenic fibroma (POF) (WHO type) or peripheral ameloblastoma are reported. Their immunohistochemical characteristics were investigated in an attempt to clarify their histogenesis. The results showed that the epithelial component of this neoplasm tended to retain its distinct odontogenic character and expressed a keratin profile different from that of the overlying oral epithelium from which both cases most probably originated. The connective tissue element of these tumors was vimentin-positive and S-100 protein negative, confirming their mesodermal nature but precluding the possibility of ectomesenchymal derivation. No reactivity for desmin was noted.