PURPOSE: To identify biologic and outcome differences between double hormone receptor (HR)-positive (dHR, estrogen receptor (ER)/progesterone receptor [PgR]) and single HR-positive (sHR, either ER/PgR or ER/PgR) breast cancer; and to explore whether hormone therapy (HT) response in HER2-negative breast cancer correlates with HR status. PATIENTS AND METHODS: This retrospective study was conducted by using 2 large breast cancer databases: the Surveillance, Epidemiology, and End Results (SEER) database and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) clinical data set. Cox regression analysis was used to estimate overall survival (OS) and breast cancer-specific survival (BCSS) among sHR and dHR patients. RESULTS: In the SEER database, dHR patients had significantly longer OS and BCSS than ER/PgR patients in short-term follow-up (OS: hazard ratio = 0.620; 95% confidence interval [CI], 0.590, 0.652; P < .001; BCSS: hazard ratio = 0.493; 95% CI, 0.462, 0.526; P < .001). Meanwhile, ER/PgR patients had younger age, larger tumor size, and higher disease grade than dHR and ER/PgR patients. In patients who received HT, dHR patients had a more favorable OS than ER/PgR patients (hazard ratio = 0.789; 95% CI, 0.635, 0.982; P = .034), and ER/PgR patients had a worse OS than ER/PgR patients at 10 years' follow-up (hazard ratio = 7.991; 95% CI, 1.053, 60.644; P = .044). However, these groups had similar outcomes over longer periods. CONCLUSION: In HER2-negative breast cancer, sHR patients are associated with relatively worse characteristics and worse short-term outcomes than dHR patients. Additionally, the outcome of patients receiving HT may differ according to the HR status. However, further studies are needed to confirm these conclusions.