With improvements in survival among individuals diagnosed and treated for cancer there is an increasing recognition of the risk of long-term adverse effects of therapy. Second neoplasms represent one of the more serious late effects of treatment and are associated with a substantial level of morbidity and mortality. Survivors of childhood cancers, because of their potential longevity, are at particular risk for this adverse outcome. The Childhood Cancer Survivor Study is a large cohort consisting of adult survivors of childhood cancer diagnosed and treated between 1970 and 1986. The CCSS has provided important data to quantify radiation-associated risk for subsequent cancers including neoplasms of the breast, thyroid and central nervous system.