Background: The prognostic impact of tumor location on breast cancer patients is not consistent and still controversial. We aimed to investigate the prognostic role of primary tumor location on the survival of patients with breast cancer. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified 53,905 patients diagnosed with tumors in the lower quadrants (n=11,065), upper quadrants (n=38,974), or central and nipple (n=3,866). Chi-squared test was used to compare categorical variables across the groups. Cox proportional hazard models were applied to estimate the factors associated with prognosis.Results: Compared with the other quadrants, patients with central and nipple lesions showed generally more unfavorable clinicopathologic features and worse breast cancer-specific survival (BCSS) and overall survival (OS). Multivariate Cox analysis showed a higher hazard ratio (HR) for tumor location of central and nipple (BCSS: HR, 1.145, p = 0.036, 95% confidence interval [CI], 1.009-1.299; OS: HR, 1.118, p = 0.024, 95% CI: 1.015-1.232), while lower HR were observed for upper quadrants (BCSS: HR, 0.888, p = 0.004, 95% CI: 0.818-0.964; OS: HR, 0.930, p = 0.023, 95% CI: 0.873-0.990). Multivariate logistic regression indicated that tumors located in central and nipple were more likely to be inoperable disease (HR, 1.460, 95% CI: 1.300-1.640, p < 0.001), while tumors located in upper quadrants tend to be operable disease (HR, 0.895, p = 0.005, 95% CI, 0.829-0.967).Conclusion: Tumors located in central and nipple had negative contact with BCSS and OS, while tumor located in upper quadrants had favorable contact with survival.