Melanoma incidence continues to increase despite public education measures to limit sun exposure. This is the first prospective study evaluating dietary PCB exposure and melanoma. PCB exposure—mainly from fatty fish—was associated with a four-fold increased risk of melanoma. Eicosapentaenoic acid and docosahexaenoic acid intake was associated with 80% lower risk of melanoma. Adequately balancing the risk and benefits of fish consumption is a key public health issue.