We prospectively screened (through chart review) 913 consecutive patients who were seen at the Massachusetts General Hospital (MGH) Melanoma Clinic over a 6-month period (December 1997 to August 1998) and identified 519 patients with invasive melanomas. TheMGHMelanoma Clinic is a referral-based clinic for patients with a history of melanomaand high-risk individuals with a history of atypical moles or a family history of melanoma. We identified 172 patients whowere or had been diagnosed as having an invasive or metastatic melanoma before they were 40 years old. The diagnoses did not have to have been rendered during the ascertainment period; the average interval between melanoma diagnosis and the study visit was 5.9 years (range, 0 [time at diagnosis] to 30 years). Only diagnoses that were histologically confirmed by a member of the MGH Dermatopathology Unit were included. Patients with a diagnosis of melanoma in situ were excluded, given the occasional ambiguity between melanoma in situ and severely dysplastic nevus. At the time of the clinic visit, each of the 172 patients was provided with a detailed letter describing the study. Those patients expressing interest then underwent an extended discussion regarding the study content and risks. A total of 49 patients (28%) consented to the study and, in accordance with a protocol approved by the Dana Farber Cancer Institute and theMGHInstitutional Review Board, donated 20mLof blood for genetic analysis. The blood samples were coded, and the confidentiality of the patients was maintained. The results were not available to the patients. Medical and family histories and demographic details of participants were recorded through chart review and direct interview. All 49 patients were white and were unrelated to one another. Forty-three blood specimens from normal, healthy blood donors at heMGHblood bank were used for analysis of the polymorphism.