The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18-1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27-2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32-3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70-1.84; P(interaction) = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (P(interaction) = 0.09). These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction. Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome.