Oral peripheral nerve sheath tumors (OPNSTs) are reactive or neoplastic diseases that develop from proliferation of the nerve itself or their limiting sheaths. Here we describe the clinicopathologic data of OPNSTs observed in a sample of the Brazilian population and evaluate the expression of molecules associated with neural biology to determine their usefulness in the diagnosis. Descriptive study of cases diagnosed as OPNSTs, from the Pathology Laboratory at the School of Dentistry/ Federal University of Uberlandia, followed by an immunohistochemical study of S-100, CD57, neurofilament protein (NFP) and epithelial membrane antigen (EMA). OPNSTs comprised 0.27% of all biopsies. There were eight patients with neurofibromas, eight with traumatic neuromas, seven with schwannomas, five with granular cell tumor (GCT), and four with palisaded encapsulated neuromas (PEN). Women were more frequently affected (60.6% of the cases). Tongue and lips prevailed as the most frequent sites. S-100 was reactive in 100% of the cases. Neural fibers evidenced by CD57 reactivity of their Schwann cells were always nested in bundles within neurofibromas and GCT, absent within schwannomas and dispersed within PEN. Reactivity for NFP was limited to axons and then followed the same pattern of CD57, though much less evident. Reactivity for EMA was observed in the capsular tissues and perineurium of nerve fascicles, and absent in parenchymal cells of GCT. This study showed that OPNSTs are rare, widely benign and often found in tongue and lips. OPNSTs evolve from a common origin to distinct histological patterns, with eventual overlapping in their clinical and morphologic features. The arrangement of reactive residual neural fibers for CD57 can be a useful staining in the differential diagnosis of OPNSTs.