Background and Aims Centrally located breast cancer (CLBC), due to its proximity to the nipple-areolar complex, has long been treated primarily with mastectomy, while the oncologic safety of breast-conserving surgery (BCS) remains controversial. This study, based on a large-scale database combined with a real-world cohort, compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database, including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy. Propensity score matching (PSM) yielded 1 951 matched pairs, and disease-specific survival (DSS) and overall survival (OS) were compared between groups. Cox regression analyses were performed to identify prognostic factors, and subgroup analyses were conducted. Additionally, an independent validation cohort from Xiangya Hospital, Central South University (2015-2016) included 221 BCS and 636 mastectomy patients, with OS and progression-free survival (PFS) assessed.Results After PSM, baseline characteristics between groups were well balanced. Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy, and 5-, 7-, and 10-year OS rates were comparable (all P>0.05). Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease, different HER2 statuses, and those receiving chemotherapy, while in patients receiving radiotherapy, BCS showed significantly better DSS and OS than mastectomy (both P<0.05). Multivariate Cox regression identified T, N, and M stage, histologic grade, molecular subtype, ER/PR status, and chemotherapy as independent prognostic factors (all P< 0.05), whereas surgical type was not (P>0.05). The validation cohort confirmed the SEER findings, with no significant differences in OS or PFS between the two groups (both P>0.05).Conclusions BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy. These findings suggest that CLBC should not be considered a contraindication to BCS, supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.