To evaluate the potential clinical benefit on radiotherapy to supraclavicular region on patients pT1-2N1M0 breast cancer with after mastectomy. Methods: A total of 923 patients with pT1-2N1M0 treated by radiotherapy (RT) to chest wall plus supraclavicular region (supraclavicular RT group, SCRT) or RT to chest wall only (non-supraclavicular RT, NSCRT) were retrospectively analyzed. Supraclavicular fossae recurrence (SCFR) rate and overall survival (OS) rate were analyzed by Kaplan-Meier method. The risk factors for SCFR were evaluated by univariate and multivariate analysis. Results: In the following-up period (medium time: 108 months; range from 6 to 179 months), the 5-year and 10-year SCFR in the NSCRT group and the SCRT group were 3.5% and 1.5% (P=0.052), 7% and 2.6% (P=0.001), and the 5-year and 10-year OS were 81.5% and 87.3% (P=0.023), 67.9% and 78.4% (P=0.001), respectively. Univariate analysis showed that risk factors associated with SCFR were age <35 years (P=0.016), T2 stage (P=0.018), 3 axillary lymph nodes (P=0.006), progesterone receptor negative (P=0.038), and human epidermal growth factor receptor-2 positive (P=0.01). Multivariate analysis further demonstrated that T2 stage and age<35, with 3 positive axillary lymph nodes were SCFR-independent prognostic factors. Analysis was conducted by grouping patients with any two of the three items as a high-risk group and patients without or with only one of the three conditions as a low-risk group. RT in the supraclavicular region significantly reduced the 10-year SCFR in the high-risk group (NSCRT, 30.2%; SCRT, 4.5%, P<0.001). However, this benefit was not obvious in the low-risk group (NSCRT, 4%; SCRT, 1.8%, P=0.063). Conclusion: RT in supraclavicular region should be recommended to pT1-2N1M0 breast cancer patients with two of the three items (<35 years, T2 stage diseases, and 3 axillary lymph node metastasis). High-risk patients need SCRT; whereas the low-risk patients do not need.