PNL2 is a novel monoclonal antibody that labels melanocytes in the cytoplasm and plasma membrane and tumors derived from these cells (melanomas and clear cell sarcomas). Antibodies against PNL2, Melan-A and HMB-45 stain most clear cell sarcoma cells and a few cells in angiomyolipomas and lymphangioleiomyomatosis; a panel of antibodies, including HMB-45, MART-1, Tyrosinase, and MiTF enables differential diagnosis. Anti-PNL2 may be most useful because of its high sensitivity for metastatic melanoma, and combined with antibodies against S-100 and HMB-45 is a highly sensitive and specific marker for mucosal melanoma.