This study aimed to investigate the prognostic value of biological factors, including histological grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status in de novo stage IV breast cancer. Based on eligibility, patient data deposited between 2010 and 2014 were collected from the surveillance, epidemiology, and end results database. The receiver operating characteristics curve, Kaplan–Meier analysis, and Cox proportional hazard analysis were used for analysis. We included 8725 patients with a median 3-year breast cancer-specific survival (BCSS) of 52.6%. Higher histologic grade, HER2-negative, ER-negative, and PR-negative disease were significantly associated with lower BCSS in the multivariate prognostic analysis. A risk score staging system separated patients into four risk groups. The risk score was assigned according to a point system: 1 point for grade 3, 1 point if hormone receptor-negative, and 1 point if HER2-negative. The 3-year BCSS was 76.3%, 64.5%, 48.5%, and 23.7% in patients with 0, 1, 2, and 3 points, respectively, with a median BCSS of 72, 52, 35, and 16 months, respectively (P < 0.001). The multivariate prognostic analysis showed that the risk score staging system was an independent prognostic factor associated with BCSS. Patients with a higher risk score had a lower BCSS. Sensitivity analyses replicated similar findings after stratification according to tumor stage, nodal stage, the sites of distant metastasis, and the number of distant metastasis. In conclusion, our risk score staging system shows promise for the prognostic stratification of de novo stage IV breast cancer.