Locally advanced breast cancer (LABC) is a disease that is heterogeneous in its presentation, potentially curable, and generally necessitating multidisciplinary management. Radiation therapy (RT) plays an important role in the management of LABC. The integration of radiation with surgery, chemotherapy, and sometimes breast reconstruction can be complex. The American College of Radiology Appropriateness Criteria Breast Committee aims to provide guidance for the management of a variety of LABC cases. The American College of Radiology Appropriateness Criteria is evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment.