Because mucosal melanoma of the head or neck is uncommon, retrospective data are of value in defining its natural history, response to treatment, and patterns of recurrence. We analyzed the medical records of 28 patients who had been treated for a mucosal melanoma of the head or neck between 1961 and 1993. We found that their cumulative 5-year survival rate was 20%. Patients who had primary tumors of the nasal cavity had significantly better 5-year survival than other patients. Early stage at presentation was another predictor of a more favorable outcome. Only 2 of the 17 patients (12%) who underwent surgery died with local disease. However, 13 of these 17 surgical patients (76%) eventually died of distant metastases. There were 3 long-term (> 5 yr) survivors: 2 who were treated by surgery alone, and 1 who was treated with surgery and radiation therapy. We found that aggressive resection of the primary tumor and of any local recurrence can achieve local control in most patients with mucosal melanoma of the head or neck. Distant metastasis is the limiting factor for long-term survival.