The melanoma-associated antigen (MAGE) family consists of a number of antigens initially recognized by cytotoxic T lymphocytes, which are currently being investigated for immunotherapy of patients with metastatic melanoma and other tumor types. Expression of MAGE mRNA in melanocytic tumors is said to be restricted to invasive malignant tumors and absent in nevi. Recently, a monoclonal antibody (57B) has become available to examine MAGE protein expression in archival material. In this study, we performed immunohistochemical analysis on 132 melanocytic nevi and 205 melanomas (85 primary cutaneous melanomas and 120 metastatic tumors) to determine the frequency of MAGE expression and to explore a potential correlation with various prognostic parameters. None of the melanocytic nevi and none of the 20 in situ melanomas was immunopositive with the antibody 57B. Immunoreactivity was present in 17 of 65 (26%) primary invasive melanomas of the skin and in 30 of 120 (25%) metastatic tumors. Positive immunostaining did not correlate with tumor stage (P = .66), Breslow thickness (P = .39), Clark level (P = .5), or the histologic type of melanoma (P = .23) but was associated with a brisk infiltrate of lymphocytes involving the vertical growth phase of melanomas (P = .01). Because tumor-infiltrating lymphocytes in melanoma are associated with longer survival, our findings suggest a potential prognostic role for MAGE. Furthermore, the seeming restriction of immunopositivity to invasive malignant tumors suggests a potential diagnostic role for the antibody 57B in confirming the malignant potential of a melanocytic tumor.