Objective To investigate the prognostic differences and decision-making role in postoperative radiotherapy of four molecular subtypes in pT1-2N1M0 stage breast cancer. Methods The clinicopathological data of 1526 patients with pT1-2N1M0 breast cancer treated at West China Hospital of Sichuan University between 2008 and 2018 were retrospectively analyzed. χ2 test was used to compare the clinicopathological features among patients with different molecular subtypes. Kaplan-Meier survival analysis and log-rank test were used to draw the survival curves and compare the overall survival (OS) and breast cancer-specific survival (BCSS) among patients with different molecular subtypes. Cox regression model was used to determine the influencing factors of OS of patients after radical mastectomy. Results Among the 1526 patients with pT1-2N1M0 breast cancer, there were 674 cases (44.2%) of Luminal A subtype, 530 cases (34.7%) of Luminal B subtype, 174 cases (11.4%) of human epidermal growth factor receptor 2 (Her-2) overexpression subtype, and 148 cases (9.7%) of triple-negative subtype. The 5-year OS rates of Luminal A, Luminal B, Her-2 overexpression and triple negative patients were 98.6%, 94.3%, 95.5% and 91.2%, respectively (χ2=11.712, P=0.001), and the 5-year BCSS rates were 99.3%, 94.6%, 95.5% and 92.5%, respectively (χ2=18.547, P<0.001). Multiple Cox regression analysis showed that menstrual status [hazard ratio (HR)=0.483, 95% confidence interval (CI) (0.253, 0.923), P=0.028] and whether endocrine therapy [HR=2.021, 95%CI (1.012, 4.034), P=0.046] were prognostic factors for the 5-year OS rate of breast cancer patients after radical mastectomy (P<0.05). However, it failed to reveal that Luminal subtypes and postoperative radiotherapy were prognostic factors for the 5-year OS rate (P>0.05). Conclusions In pT1-2N1M0 breast cancer patients, the 5-year OS rate and 5-year BCSS rate in triple-negative patients are the lowest. The relationship between Luminal classification, postoperative radiotherapy and survival in patients after radical mastectomy needs further study in the future.