Anti-PNL2 is a novel monoclonal antibody, which has recently been introduced as an immunohistochemical reagent to stain melanocytes and tumors derived therefrom. The antigen recognized by PNL2 is different from Melan A and gp100. Its epitope is not destroyed by digestion with neuraminidase i.e. its epitope id not glycosylated. Anti-PNL2 may be most useful because of its high sensitivity for metastatic melanoma (87%), as opposed to 76% for anti-HMB45 and 82% for anti-MART-1. Anti-PNL2 labels intra-epidermal nevi while the dermal component of compound nevi are largely non-reactive with anti-PNL2. Antibodies against PNL2, MART-1 (Melan A) and HMB45 stain most clear cell sarcoma cells and a few cells in angio-myolipomas and lymphangioleiomyomatosis. Anti-PNL2 is a useful antibody for the identification of melanomas and clear cell sarcomas. Differential diagnosis is aided by the results from a panel of antibodies, including antibodies against HMB45, MART-1, tyrosinase, and MiTF.