In 7 melanoma-prone families, pigmented lesions with distinctive clinical and histologic characteristics occurred in 18 of 20 melanoma patients (90%) and 24 of 43 1st-degree relatives (56%). Recognition of these lesions led to the detection of early-stage melanoma in 6 family members. This syndrome appears to represent an autosomal dominant trait and may serve as a cutaneous marker to identify persons at high risk for melanoma.