OBJECTIVES: To explore the relationship between level and type of comorbidity and guideline-concordant care for early-stage breast cancer. DESIGN: Cross-sectional. SETTING: National Program of Cancer Registry (NPCR) Breast and Prostate Cancer Patterns of Care study, which re-abstracted medical records from 2004 in seven cancer registries. PARTICIPANTS: Individuals with stage 0-III breast cancer. MEASUREMENTS: Multicomponent guideline-concordant management was modeled based on tumor size, node status, and hormone receptor status, according to consensus guidelines. Comorbid conditions and severity were measured using the Adult Comorbidity Evaluation Index (ACE-27). Multivariate logistic regression models determined factors associated with guideline-concordant care and included overall ACE-27 scores and 26 separate ACE comorbidity categories, age, race, stage, and source of payment. RESULTS: The study sample included 6,439 women (mean age 58.7, range 20-99; 76% white; 44% with no comorbidity; 70% estrogen- or progesterone-receptor positive, or both; 31% human epidermal growth factor receptor 2 positive). Care was guideline concordant in 60%. Guideline concordance varied according to overall comorbidity burden (70% for none; 61% for minor; 58% for moderate, 43% for severe; P < .05). In multivariate analysis, the presence of hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.01-1.30) predicted guideline concordance, whereas dementia (OR = 0.45, 95% CI = 0.24-0.82) predicted lack of guideline concordance. Older age (≥ 50) and black race were associated with less guideline concordance, regardless of comorbidity level. CONCLUSION: When reporting survival outcomes in individuals with breast cancer with comorbidity, adherence to care guidelines should be among the covariates.