In a series of 1341 patients with histologically proven malignant melanoma seen at Duke University Medical Center from 1968 to 1978, 107 patients developed central nervous system (CNS) metastases. These patients were evaluated on the basis of which factors were associated with the development of CNS metastases. Male patients, patients with invasive primary lesions as measured by Clark's system, and patients with primary lesions of the head/neck or oral mucosa had higher incidences of CNS metastasis. Age and race were not significant factors. Clinically, single CNS metastases were seen in 48.8% of the patients; multiple cerebral lesions were seen in 37.2% of the patients. In 22% of the patients there was CNS metastasis alone, in 41% a second organ was involved, and in 20% three organs were involved.