Background: This study investigated the survival benefit of radiotherapy (RT) of the supra- and infraclavicular lymphatic drainage area in Chinese women with T1-2N1M0 breast cancer receiving mastectomy. Methods: A total of 593 cases were retrospectively reviewed from 1998 to 2007. The relationship between supra- or infraclavicular fossa relapse (SCFR) and post-operative RT at the supra-/infraclavicular lymphatic drainage area was evaluated. Results: The majority of patients (532/593; 89. 8%) received no RT while 61 patients received RT. The median follow-up was 85 months. Among patients without RT, 54 (10. 2%) developed recurrence in the chest wall or ipsilateral SCFR. However, none of the 61 patients who underwent RT demonstrated SCFR. One patient who received RT (1. 6%) experienced recurrence in the chest wall. Univariate analysis revealed that age and molecular subtype (both P < 0. 05) were two prognostic factors related to supraclavicular and infraclavicular fossa relapse-free survival (SFRFS). Multivariate analysis revealed that only Her-2 positive status (P = 0. 011) was an independent predictor of SFRFS. RT had no influence on distant metastasis (P = 0. 328) or overall survival (P = 0. 541). SCFR significantly affected probability of distant metastasis (P < 0. 001) and overall survival (P < 0. 001). Conclusion: Although RT was not significantly associated with SFRFS, postoperative RT was significantly associated with a lower locoregional (i. e., supraclavicular/infraclavicular and chest wall) recurrence rate. SCFR significantly influenced distant metastasis-free survival, which significantly influenced the overall survival of T1-2N1M0 breast cancer patients after mastectomy. Thus, prophylactic RT is recommended in T1-2N1M0 breast cancer patients, especially those who have Her-2 positive lesions.