BACKGROUND: A history of multiple primary melanomas (PMs) has been associated with improved survival in patients with early stage melanoma, but whether it also is correlated with survival in patients with metastatic melanoma is unknown. The authors sought to address the latter question in the current study. METHODS: Patients with metastatic melanoma diagnosed at the Melanoma Institute Australia between 1983 and 2008 were identified. Overall survival (OS) was calculated from date of first distant metastasis. Survival analysis was performed using the Kaplan-Meier method, log-rank tests, and multivariate Cox proportional hazards models. RESULTS: Of 2942 patients with metastatic melanoma, 2634 (89.5%) had 1 PM and 308 (10.5%) had >1 PM. Factors that were associated independently with shorter OS were site of metastasis, including the brain (hazard ratio [HR], 2.41; 95% confidence interval [CI], 2.07-2.81; P <.001) and nonlung viscera (HR, 1.92; 95% CI, 1.67-2.22; P <.001, vs lymph node/subcutaneous/soft tissue), age >60 years (HR, 1.23; 95% CI, 1.12-1.36; P <.001), shorter disease-free interval from PM to first distant metastasis (≤12 months vs >36 months: HR, 1.62; 95% CI, 1.39-1.89; P <.001), and fewer PMs (1 vs ;gt HR, 1.26; 95% CI, 1.08-1.47; P =.004). CONCLUSIONS: A history of multiple PM was an independent predictor of improved survival for patients with metastatic melanoma. The results indicate that a history of multiple PMs should be incorporated into multivariate analyses of prognostic factors and treatment outcomes. Cancer 2012.