Background: There is no clear evidence of a survival benefit of primary tumor resection in patients with stage IV breast cancer (BC). This large study evaluated factors associated with undergoing primary tumor resection, and whether resection at the primary site, or distant site resection (metastasectomy), was associated with better overall survival (OS). Methods: This retrospective analysis of stage IV BC cases used the 2004-2016 National Cancer Database (NCDB) population. To evaluate variables associated with primary tumor resection, we used univariate analyses (chi-squared and Wilcoxon rank-sum test), followed by multivariate logistic regression. Consequently, we conducted multivariate Cox regression survival analyses on the following groups: 1) all stage IV BC patients; 2) a subset of those with only 1 site of metastasis; and 3) another subset with metastasis to > 1 distant site. Results: A total of 54,871 stage IV BC patients were included in this analysis. From this, we analyzed a subset with only 1 distant site involved (n = 30,480) and another subset with multiple secondary sites (n = 17,344). In total, 15,661 patients underwent surgery at the primary site: 11,451 (73.1%) were non-Hispanic white; 2479 (15.8%) were non-Hispanic black; 981 (6.3%) were Hispanic and 484 (3.1%) were Asian. Variables associated with undergoing resection of the primary tumor were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N-staging, extent of metastasis and year of diagnosis. Survival analysis of all stage IV patients showed that both lumpectomy (HR 0.59, 95% CI: 0.57-0.62, p < 0.0001) and mastectomy (HR 0.62, 95% CI: 0.60-0.64, p < 0.0001) were associated with better OS when compared to no surgery. The statistical effect was larger in the subgroup with metastasis to 1 site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit compared to no metastasectomy across all 3 groups. In the subgroup with metastasis to only 1 site, metastasectomy was associated with better OS when the metastatic site was liver (HR 0.60, 95% CI: 0.43-0.82, p = 0.0018), lung (HR 0.47, 95% CI: 0.37-0.61, p < 0.0001), and brain (HR 0.70, 95% CI: 0.55-0.88, p = 0.0022). Conclusions: Across all 3 patient subgroups, primary tumor resection (lumpectomy or mastectomy) and metastasectomy were associated with improved OS. Additional stratified analysis in the subgroup with only 1 metastatic site showed benefit of metastasectomy when that site was the lung, liver or brain.