Objective: Limited data are available regarding estrogen receptor (ER) negative progesterone receptor (PR) positive (ER-PR+) breast cancer, resulting in difficult treatment decision and survival forecast for this breast can-cer subtype. This study aimed at evaluating the clinical characteristics and survival outcomes of patients with ER-PR+ breast cancer, taking into account human epidermal growth factor receptor 2 (HER2) status. Patients and Methods: We identified female breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database with a median follow-up period of 60 months from 2010 to 2012, and these patients were classified into four subtypes according to ER and PR expression, as ER+PR+, ER+PR-, ER-PR+, and ER-PR-. ER+PR- subtype was further stratified based on HER2 status. Kaplan-Meier survival plots and Cox regression models were applied to evaluate overall survival (OS) and breast cancer specific survival (BCSS) outcomes differences among breast cancer subtypes. Results: Of 140,072 female breast cancer patients included in the study, 98,721 (70.48%) were ER+PR+, 16,581 (11.84%) were ER+PR-, 1,579 (1.01%) were ER-PR+, and 23,241 (16.59%) were ER-PR-. ER-PR+ patients had significantly poorer OS and BCSS than ER+PR+ and ER+PR- patients. Compared to those diagnosed with other subtypes, ER-PR+ patients were more likely to be younger, and to have higher rate of HER2 positive status, stage IV tumor, positive lymph node status, and tumor size of 21-50 mm. HER2 negativity was found to be a significant predictor of poor prognosis in terms of both OS and BCSS in ER-PR+ patients. Conclusions: We found that ER-PR+ tumors represented the smallest distinct biological subtype, with poorer survival outcomes compared to ER+PR+ and ER+PR- subtypes. Moreover, ER-PR+ patients with HER2 negative breast cancer were associated with poorer OS and BCSS compared to ER-PR+ patients with HER2 positive breast cancer. These findings may help to optimize treatment and improve outcomes for ER-PR+ patients.