Purpose: The risk of breast cancer is high in women treated for a childhood cancer with chest irradiation. We sought to examine variations in risk resulting from irradiation field and radiation dose. Patients and Methods: We evaluated cumulative breast cancer risk in 1,230 female childhood cancer survivors treated with chest irradiation who were participants in the CCSS (Childhood Cancer Survivor Study). Results: Childhood cancer survivors treated with lower delivered doses of radiation (median, 14 Gy; range, 2 to 20 Gy) to a large volume (whole-lung field) had a high risk of breast cancer (standardized incidence ratio [SIR], 43.6; 95% CI, 27.2 to 70.3), as did survivors treated with high doses of delivered radiation (median, 40 Gy) to the mantle field (SIR, 24.2; 95% CI, 20.7 to 28.3). The cumulative incidence of breast cancer by age 50 years was 30% (95% CI, 25 to 34), with a 35% incidence among Hodgkin lymphoma survivors (95% CI, 29 to 40). Breast cancer-specific mortality at 5 and 10 years was 12% (95% CI, 8 to 18) and 19% (95% CI, 13 to 25), respectively. Conclusion: Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.