We present 14 patients with primary sinonasal melanomas (SM) identified from 1984–1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39–88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.