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Objective To calculate survival probabilities of patients with 3 or more multiple primary melanomas. Design Retrospective cohort study of patients with primary melanoma. Setting Patients treated at a tertiary center (Sydney Melanoma Unit, Sydney, Australia) for stage I or II melanoma between 1983 and 1999. Patients From 5250 patients with primary melanoma, 264 (5.0%) had double and 34 (0.6%) had 3 or more primary melanoma lesions. Results The estimated 10-year risk for developing a second primary melanoma in these patients was 12.7% (95% confidence interval [CI], 10.5%-14.9%). For those patients who had 2 primary melanomas, the estimated 10-year risk of developing a third lesion was 27.7% (95% CI, 14.7%-36.7%). When controlling for known prognostic factors in a proportional hazards regression model, the number of primary melanomas was a significant favorable survival predictor when the thickest or the first tumor was modeled. In patients with 3 or more primary melanomas, 31 survived when 25 (95% CI, 22-27) were expected to survive. Patients who survive longer may have the opportunity to develop multiple primary melanomas. Patients who encountered all their primary lesions within 2 years may not be subject to this bias. Within the 3 or more melanoma set, 11 patients had all primary melanomas within 2 years. All survived, whereas 9 (95% CI, 8-10) were expected to survive. Conclusions Patients with 3 or more primary melanoma lesions survive longer than anticipated. Such enhanced survival in patients with 3 or more primary melanomas may be consistent with observations of an "immunization effect" in animals inoculated with multiple tumors.