To examine whether individuals with a history of malignancy are at increased risk for uveal melanoma developing, the authors conducted a case-control study comparing history of prior malignancy among 197 New England cases and 385 matched controls identified by random digit dialing (RDD), and 337 cases residing within the United States and 800 sibling controls. Estimated relative risks for uveal melanoma associated with nonskin cancers were 1.2 (95% confidence interval [Cl], 0.61-2.3) and 0.9 (95% Cl, 0.49-1.5) for RDD and sibling comparisons, respectively. Prior skin malignancy (melanoma and basal or squamous cell types) tended to increase the estimated risk in both groups (case/RDD comparison: relative risk, 1.5; 95% Cl, 0.67-3.5 and case/sibling comparison: relative risk, 1.7; 95% Cl, 0.93-2.9). Among females, history of a malignancy was associated with a higher risk in the case/RDD comparison only (relative risk estimate, 2.2; 95% Cl, 0.97-5.1). These results suggest that the association of prior malignancies with uveal melanoma is weak. Cutaneous malignancies and uveal melanomas may share some common risk factors.