BACKGROUND: Systemic therapy (ST) is essential for de novo stage IV breast cancer (BC). Stage IV BCs are highly heterogeneous, and it seems inappropriate to treat all de novo stage IV BCs equally. The survival benefit of surgery for primary sites in patients with de novo stage IV BC remains inconclusive. PATIENTS AND METHODS: We investigated 220 patients with clinical de novo stage IV BC. The relationship between primary site surgery and overall survival (OS) was analyzed. Factors such as tumor subtype, timing of surgery, and efficacy of ST were also evaluated. RESULTS: The median follow-up time was 37.9 (0.5-201.7) months. In the total cohort, the median OS of the patients with and without primary site surgery was 70.5 months (95% confidence interval [CI] 58.4-107.3) and 42.7 months (95% CI 35.7-48.8), respectively. The OS was significantly longer in patients who underwent primary site surgery, especially in the hormone receptor (HR) + /HER2- and HER2 + subtypes, but not in the triple-negative subtype. OS prolongation was significant in patients who underwent surgery ≥ 24 months after the first diagnosis and in whom the first-line ST was effective for ≥ 24 months. Primary site surgery was a good prognostic factor in both univariate and multivariate analyses. CONCLUSIONS: The OS was significantly longer in patients with de novo stage IV BC who underwent primary site surgery than in those who did not undergo surgery. Our results suggest that the tumor subtypes, efficacy of ST, and timing of surgery influenced the benefits of surgery.