Women undergoing breast reduction surgery have been reported to be at low subsequent risk of breast cancer, especially when the surgery is performed after age 40. To evaluate the age and time-related patterns of cancer risk following surgical removal of breast tissue, we identified 31,910 women who underwent breast reduction surgery from 1965 to 1993 in Sweden using hospital discharge register data. There were 19,975 women (63 percent) under age 40 at surgery. Linkages with Swedish registries for cancer, death, and emigration were based on unique national registration numbers assigned to each Swedish resident. Cancer incidence was contrasted with that expected in the general population based on age- and calendar year-specific data from the nationwide cancer registry. Overall, 161 incident breast cancers were identified during 238,765 person-years of observation (mean, 7.5 years) compared with 223.9 expected (standardized incidence ratio = 0.72; 95 percent confidence interval = 0.61 to 0.84). The reduction in risk of breast cancer was most pronounced for women whose operations were performed after age 50 (SIR = 0.57) and for those followed for more than 5 years (SIR = 0.68). Among women operated on before age 40, risk was nonsignificantly elevated within the first 5 years after surgery (SIR = 1.47; 95 percent CI = 0.89 to 2.30) but tended to be reduced thereafter (SIR = 0.80; 95 percent CI = 0.55 to 1.13). The magnitude of the reduction in risk thus appears directly related to age at surgery. Women followed for an average of 7.5 years after bilateral breast reduction surgery, were at a statistically significant 28 percent decreased risk of breast cancer. The current study is thus consistent with a protective effect following partial removal of breast glandular tissue.