Primary melanocytic neoplasms of the central nervous system (CNS) consist of a spectrum ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Diagnostically difficult intermediate lesions lie between these extremes. Clinicopathologic features of 33 cases were studied to define histologic appearances, diagnostic criteria, and the clinical behavior of lesions along this spectrum. Seventeen cases were well-differentiated, solitary leptomeningeal tumors classified as melanocytomas. They contained variably pigmented melanocytic cells arranged in tight nests, sheets, or fascicles. Mitotic rates ranged from zero to one per 10 high-power fields (HPFs), with most having zero per 10 HPFs. All tumors were immunoreactive for HMB-45 and S-100 protein and negative for epithelial membrane antigen. MIB-1 staining was low (<1-2%). Nuclei were regular, often with small, eosinophilic nucleoli. These lesions arose predominantly in the spinal canal (65%) in patients ranging in age from 17 to 73 years. None recurred after surgical resection. In contrast to these benign lesions, there were 13 cases with histologic and cytologic features consistent with those of malignant melanoma. These cases contained larger, cytologically atypical, pigmented tumor cells growing in loose nests or sheets, often with CNS invasion or necrosis. Some contained bizarre, pleomorphic nuclei; others were densely cellular and mitotically active, but less pleomorphic. Mitotic rates (mean, 5.7 per 10 HPFs) and MIB-1 labeling indices (mean, 8.1%) were higher than those of melanocytomas. Melanomas occurred at spinal (38%), posterior fossa (38%), and supratentorial (23%) levels in patients ranging in age from 15 to 71 years. After resection, 8 of 13 lesions recurred, with four being fatal (mean survival, 14 months). Of five totally resected melanomas, four did not recur (mean follow-up, 26 months). Three intermediate-grade melanocytic tumors could not be classified as melanocytoma or melanoma. All showed sheetlike growth patterns, microscopic CNS invasion, and occasional mitoses. MIB-1 staining ranged from 1% to 4%. One tumor recurred after 17 months; one patient was lost to follow-up after 5 months; and the third died after surgery. Although melanocytic tumors represent a spectrum of lesions, certain histopathologic features are helpful in predicting biologic behavior.