Despite the excellent survival for children with retinoblastoma (Rb), survivors with a germline mutation in their Rb-1 gene (hereditary Rb) are prone to subsequent cancers including sarcomas, melanoma, and cancers of the brain and nasal cavity, and radiotherapy appears to increase the risk, suggesting a gene-environment interaction. Cancer incidence and mortality continues to be monitored in the largest cohort of Rb survivors in the United States. Analysis of mutations in the Rb-1 gene have been in progress and Rb patients, who have developed a melanoma, and their first degree relatives, have been examined clinically for dysplastic nevi. Rb survivors were interviewed in 2000 to obtain cancer risk factor data. Cancer screening practices and smoking behavior have been evaluated in this cohort. Analyses of additional cancer risk factors and current health is ongoing. Newsletters informing the cohort about progress of the cohort study, their second cancer risk and cancer screening recommendations have been sent periodically to the cohort. The cohort was recently expanded to include and evaluate newer treatments for Rb patients diagnosed from 1984-2006.