Numerous studies to date have suggested an association between radiation exposure and the development of soft tissue sarcoma. The current study was performed to quantify the risk of soft tissue sarcoma in the vicinity of previously irradiated anatomic regions in women with breast carcinoma. In this population-based, retrospective cohort study, 194,798 women who were diagnosed with invasive breast carcinoma (exclusive of those with distant metastasis) between 1973--1995 were identified, and subsequent soft tissue sarcoma cases utilizing the data from the Surveillance, Epidemiology, and End Results Program (SEER) were ascertained. Poisson regression analysis was used to calculate age standardized incidence ratios (SIR) and to model the influence of radiotherapy (RT) on the relative risk (RR) between the RT and non-RT cohorts. A total of 54 women in the RT cohort and 81 women in the non-RT cohort subsequently developed soft tissue sarcoma. In the RT cohort, the SIR was 26.2 (95% confidence interval [95% CI], 16.5--41.4) for angiosarcoma and was 2.5 (95% CI, 1.8--3.5) for other sarcomas; in the non-RT cohort, the SIRs were 2.1 (95% CI, 1.0--4.4) and 1.3 (95% CI, 1.0--1.7), respectively. The RT cohort demonstrated a higher risk of developing both angiosarcoma (RR: 15.9; 95% CI, 6.6--38.1) and other sarcomas (RR: 2.2; 95% CI, 1.4--3.3) compared with the non-RT cohort, and the largest increase was observed in the chest wall/breast. The elevated RR was significant even within 5 years of RT, but it reached a maximum between 5--10 years. The risk of soft tissue sarcoma, especially angiosarcoma, was elevated after RT in women with breast carcinoma. Copyright 2001 American Cancer Society.