Introduction Breast-conserving surgery (BCS) and mastectomy are the cornerstone surgical options for invasive breast cancer, yet their comparative effectiveness in real-world practice, especially when stratified by molecular subtype, remains inadequately characterized. In light of this, we conducted a single-center retrospective cohort study to evaluate clinicopathological features, treatment patterns, and overall survival (OS) among patients undergoing lumpectomy versus mastectomy at a tertiary care center in Greece. Methods A total of 119 women treated between 2010 and 2020 were included: 79 (66.4%) underwent lumpectomy and 40 (33.6%) underwent mastectomy. Clinicopathological variables [tumor size, histologic grade, stage, lymphovascular invasion (LVSI), nodal status, molecular subtype] and adjuvant therapies [chemotherapy, radiotherapy, sentinel lymph node biopsy (SLNB), axillary lymphadenectomy] were compared between groups. Survival analyses were performed using Kaplan-Meier estimates with log-rank tests and a multivariable Cox proportional hazards regression. Results Compared with the lumpectomy group, patients selected for mastectomy more frequently presented with tumors >2 cm [29/40 (72.5%) vs. 21/79 (26.6%), p<0.001], grade 3 disease [10/40 (25.0%) vs. 21/79 (26.6%), p=0.006], stage ≥2 [31/40 (77.5%) vs. 19/79 (24.0%), p<0.001], LVSI [20/40 (50.0%) vs. 21/79 (26.6%), p=0.011], and nodal involvement [20/40 (50.0%) vs. 9/79 (11.4%), p<0.001]. The distribution of molecular subtypes differed between groups (p=0.037), with luminal B-HER2 being most common overall [46/119 (38.7%)]. Radiotherapy was administered to all lumpectomy patients [79/79 (100.0%)] versus 10/40 mastectomy patients (25.0%, p<0.001). Kaplan-Meier analysis showed superior OS in the lumpectomy cohort (log-rank p=0.001); however, multivariable adjustment identified only higher clinical stage as an independent predictor of mortality [hazard ratio (HR) per stage increment: 8.32; 95% confidence interval (CI): 2.28-30.38; p<0.01], whereas type of surgery did not remain significant. Conclusions In our cohort of 119 patients, BCS yielded excellent survival outcomes in early-stage, lower-risk tumors, whereas mastectomy was more often reserved for more advanced disease. Clinical stage at diagnosis, rather than surgical approach per se, emerged as the primary determinant of OS. Integration of molecular subtype into surgical decision-making may further refine personalized treatment strategies.