Immunostains play a limited role in the diagnosis of malignant peripheral nerve sheath tumor (MPNST). Positivity for S-100 protein in MPNST (50% to 80% of cases) is focal and not strong, except in the epithelioid variant. If there is strong, diffuse S-100 positivity in a malignant spindle cell neoplasm, the possibility of malignant melanoma should be considered. S-100 expression can also be seen in synovial sarcoma. The diagnosis of MPNST is favored if there is positivity for S-100, nestin, HMGA2, and SOX10. Elevated expression of markers such as Ki-67 and p53 have been suggested as prognostic markers for MPNST.