Background: The survival of men diagnosed with prostate cancer (PCa) has increased substantially over time, with 5- and 10-year relative survival at 100% and 99.7%, respectively. PSA screening has also led to earlier detection of disease at younger ages. This increased longevity leaves patients at future risk of second cancers. Methods: Surveillance, Epidemiology and End Results Program (SEER13) data were used to estimate the risk of second primary malignancies in a population-based cohort of 407,781 men diagnosed with PCa. SEER*Stat software was used to calculate standardized incidence ratios (SIR) for men who survived ≥ 2 months after PCa diagnosis. Results: Risk of second cancers among PCa survivors differed significantly from that observed in the U.S. general population (Table). Results also differed by race with White patients having significantly reduced risk of liver, lung and bronchus, oral cavity and pharynx, stomach, esophagus, leukemia, pancreas, and colon malignancies and significantly increased risk of melanoma, bladder, kidney, thyroid cancer, and non-Hodgkin lymphoma. Black patients shared significantly lower lung and bronchus cancer risk, but had significantly increased risk of kidney, small intestine, brain, bladder, colon and hematologic malignancies including myeloma and leukemia. Men aged 20-54 years at PCa diagnosis were at notably increased risk of subsequent breast cancer (SIR=2.79, 95% CI 1.34, 5.13) especially compared to those >55 years. Results did not differ by year of PCa diagnosis (1992-1999 vs. 2000-2007). Conclusions: Cancers that occur together may suggest novel strategies for identifying genetic and environmental risk factors for prostate cancer. These results also highlight important risks that exist for the growing population of prostate cancer survivors.