BACKGROUND: To evaluate the significance and benefit of radiotherapy (RT) in young early-stage breast cancer patients according to different molecular subtypes. METHODS: We conducted a retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results database with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status. Female patients aged 18-45, received RT treatment, and diagnosed with stage T1-3, N0-3, M0 primary breast cancer between 2010 and 2013 were identified. RESULTS: Of all the 23 148 included patients, 14 708 (63.54%), 3385 (14.62%), 1225 (5.29%), and 3830 (16.55%) were diagnosed with luminal-A (HoR + HER2-), luminal-B (HoR + HER2+), HER2-enriched (HoR-HER2+), and triple-negative (HoR-HER2-) breast cancer, respectively. RT was significantly correlated with improved overall survival (OS, HR: 0.295; 95% CI:0.138-0.63, P = 0.002) and breast cancer-specific survival (BCSS, HR: 0.328; 95% CI: 0.153-0.702, P = 0.004) in HER2-enriched patients. In addition, a significantly prolonged OS was also observed when RT was given to luminal-A (HR: 0.696; 95% CI: 0.538-0.902, P = 0.006) and luminal-B (HR: 0.385; 95% CI:0.199-0.744, P = 0.005) breast cancer patients compared to those without RT. Multivariable-adjusted analyses showed that HER2 was a significant favorable factor for RT benefit in breast cancer patients. CONCLUSIONS: RT could offer significant survival benefit in luminal-A, luminal-B, and especially HER2-enriched young early-stage breast cancer female patients. The results enabled clinicians to predict the benefits of RT and improve evidence-based treatment for breast cancer patients.