Eleven cases of palisaded, encapsulated neuroma (PEN) were studied by routine light microscopic and immunohistochemical methods. PEN showed the following staining reactions: strong, diffuse for S-100 protein (11/11) and collagen Type IV (Col. IV) (11/11); moderately strong, focal for myelin basic protein (MBP) (9/11) and Leu-7 (9/11); weak, focal for MBP (2/11), Leu-7 (2/11), neuron specific enolase (NSE) (4/11), neural filaments (NF) (5/11), epithelial membrane antigen (EMA) (6/11), and negative for glial fibrillary acidic protein (GFAP). Bielschowsky silver stain was positive in 11/11, but only four cases contained numerous axons. Col. IV and EMA stains showed a complete capsule in 1/11, incomplete capsules in 5/11 and no discernible capsules in the remainder. We concluded that (1) the immunologic profile of PEN is not specific; (2) conventional silver stain remains a suitable method to demonstrate axon-like structures; (3) the ratio of axons to Schwann cells is variable and generally less than 1:1, as previously assumed; (4) MBP and Leu-7 coexpression in Schwann cells suggests myelinization of some of the nerve fibers; (5) the pattern of EMA reaction supports perineurial cell involvement in PEN; and (6) despite the current definition of PEN, they are usually not completely encapsulated as evidenced by Col. IV and EMA strains.