Prior studies have demonstrated that adjuvant radiation therapy following mastectomy for breast cancer increases the risk of second primary esophageal cancer after 10 years, but the risk following breast-conserving surgery (lumpectomy) has yet to be determined. The authors used 1973-2000 data from the population-based Surveillance, Epidemiology, and End Results Program and estimated relative risks of 2.83 (95% confidence interval: 1.35, 5.92) and 2.17 (95% confidence interval: 1.67, 4.02) for squamous cell esophageal cancer at 5-9 and > or =10 years, respectively, following postmastectomy radiation therapy. This increase was mainly due to tumors located in the upper and middle thirds of the esophagus. No significant increase in risk was found for adenocarcinoma following mastectomy or for any type of esophageal cancer following lumpectomy. In summary, postmastectomy radiation therapy moderately increases the risk of squamous cell esophageal cancer starting 5 years after exposure, which persists after 10 years, with no increase in the risk of adenocarcinoma. This finding appears to be a function of the portals used for postmastectomy radiation therapy, which do not expose the lowest third of the esophagus, where adenocarcinomas commonly arise.