We describe the clinicopathologic characteristics of 55 oral palisaded encapsulated (solitary circumscribed) neuromas (PEN/SCN). Fifty-five cases of PEN/SCN in 54 patients were reviewed. Lesions were categorized according to their histologic pattern, partial or complete encapsulation, presence of Verocay bodies and presence of a parent peripheral nerve. In 13 selected cases immunohistochemical evaluation for neuronal markers (S-100, GFAP, NFP, EMA) was performed. When immunoreaction with EMA was weak, claudin-1 and glut-1 stains were utilized. Thirty-eight patients were men and 16 were women. Mean patient age was 48 years (SD: ±14). The vast majority involved the masticatory (palate and gingiva) mucosa (76.4%) followed by the labial mucosa, the tongue and buccal mucosa. Recurrence was recorded in only one case. Histologically, 34 lesions had a lobular pattern, 10 were plexiform, 7 fungating and 4 multilobular. Stroma was limited, but focal myxoid changes were seen at the periphery of the lobules. Only one predominantly myxoid lesion was encountered. The number of intralesional axons varied, but the ratio of Schwann cells to axons was generally less than 1:2. Most lesions (89%) were only partially surrounded by perineurium. Tumor cells were S-100 positive and GFAP negative. The parent nerve was identified in 50% of the cases. Overlying epithelium was generally atrophic. Peritumoral connective tissue was generally unremarkable, but chronic inflammation was present in five cases. PEN/SCN is a relatively common peripheral nerve sheath tumor. Generally, its diagnosis is simple. GFAP may be of help to distinguish PEN/SCN from other peripheral nerve sheath tumors (schwannoma, neurofibroma, traumatic neuroma) in cases where histomorphologic features may be confusing. Finally, pathologists should be aware of the occurrence of plexiform and multilobular PEN/SCN variants, to avoid misinterpretation as plexiform neurofibroma or schwannoma.