To investigate associations between comorbidity burden, management, and mortality in women with breast cancer. A total of 42,646 women diagnosed with breast cancer between 1992 and 2008 were identified in two Clinical Quality Registers in Central Sweden. Breast cancer-specific, conditional breast cancer, competing-cause and all-cause mortality were estimated in relation to comorbidity burden assessed by the Charlson comorbidity index. All analyses were stratified by stage at diagnosis using competing risk analyses, and all-cause mortality was estimated as a function of follow-up time. Following adjustment for age and calendar period, breast conserving surgery was significantly less likely to be offered to women with severe comorbidity (OR 0.63; 95 % CI 0.58-0.69). Similarly, the proportion treated with radiotherapy, tamoxifen, or chemotherapy was lower in women with severe compared to those with no comorbidity. In women with early stage disease, breast cancer-specific mortality was higher among patients with severe comorbidity (sHR 1.47; 95 % CI 1.11-1.94). In all stages of breast cancer, conditional breast cancer and competing-cause mortality were elevated in women with severe comorbidity. For all stages, the relative risk of all-cause mortality between women with severe versus no comorbidity varied by time since diagnosis, and was most pronounced at early follow-up. Comorbidity affects treatment decisions and mortality. In women with early stage breast cancer, severe comorbidity was associated not only with conditional breast cancer, competing-cause and all-cause mortality, but also breast cancer-specific mortality. The observed differences in breast cancer-specific mortality may be due to less extensive treatment, impaired tumor defense and differences in general health status and lifestyle factors.