Purpose: To evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement. Methods: A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjvant systemic therapy followed by breast conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy. Results: The median follow-up duration was 61 months (range, 7-173). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥4, triple negative subtype, and mastectomy were significant adverse prognosticators for DFS (p = 0.022, 0.001, 0.001, and 0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥54 Gy was not associated with DFS (5-yr rate, 52.9% vs. 50.9%, p = 0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-yr rate, 56.1% vs. 78.1%, p = 0.099) in IMN-involved patients. Conclusion: Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients. Citation Format: Kim K, Jeong Y, Shin KH, Kim JH, Ahn SD, Kim SS, Suh C-O, Kim YB, Choi DH, Park W, Cha J, Chun M, Lee DS, Lee SY, Kim JH, Park HJ. Impact of regional nodal irradiation for breast cancer patients with supraclavicular and/or internal mammary lymph node involvement: A multicenter, retrospective study (KROG 16-14) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-12.