Background: Patients with clinically diagnosed dysplastic nevi or a family history of melanoma with or without histologically diagnosed dysplastic nevi seem to be at higher risk for the development of multiple melanomas. Objective: Our purpose was to determine which factors increased the risk for the development of subsequent melanomas. Methods: This was a retrospective study in 56 patients with 157 melanomas. Results: Early age at onset (58.9%), clinically diagnosed dysplastic nevi (82.0%), a histologically diagnosed dysplastic nevus (64%), family history of clinically diagnosed dysplastic nevi (70.8%) or melanoma (64.7%) and a histologically diagnosed dysplastic nevus in combination with a family history of melanoma (48%) were found in a high percentage of patients. The mean age at diagnosis was 38.2 years. The mean interval between the first and second melanoma was 34.3 months. Of the second melanomas, 76.8% developed in a different anatomic region from the first melanomas. The mean tumor thickness (Breslow) decreased from 1.11 mm for the first melanomas to 0.90 mm for the second melanomas. Conclusion: The results suggest that genetic factors might be involved in a certain subset of patients in whom melanomas develop early and successively. (J Am Acad Dermatol 2001;44:22-7.)