Background: RSIS (CT, bone and PET scan) in pts with stage I or II BC is not recommended by NCCN and is considered optional in stage III BC. 10-15% of pts with stage III BC have occult metastases by RSIS, but it is unclear if this finding affects pt management or outcome. The addition of PET scans to conventional imaging (CT and bone scans) is of little added value (Niikura, et al. Oncologist 2011; 16: 772-82). We hypothesized that the use of RSIS in pts with stage III BC does not lead to changes in treatment or pt outcomes. Methods: After IRB approval, we retrospectively identified 875 women with stage III or stage IV BC from 2000-2010 through the Los Angeles County-University of Southern California and Norris Comprehensive Cancer Center cancer registries. Pts with clinically apparent stage IV disease, pregnancy at time of diagnosis, a history of prior malignancy, or incomplete medical records were excluded. Pts who underwent RSIS prior to planned treatment (before surgery, neoadjuvant or adjuvant therapy) were identified. RSIS results and the treatment plan in response to the results were recorded. Results: 424 pts were identified with clinical or pathologic stage III BC: 197 pts (46%) were < 50 years old, 224 (53%) had ER+ or PR+/HER2- tumors, 111 (26%) had ER-/PR-/HER2+ tumors, 74 (17%) had triple negative tumors, 15 (4%) had missing biomarker data, and 61 (14%) had inflammatory BC. 365 pts (86%) underwent RSIS. RSIS were negative for metastatic disease in 266 (73%), indeterminate in 75 (21%), and positive in 24 (7%). Treatment was altered in 21 pts (6%) based on RSIS (20 with metastatic disease, 1 with indeterminate disease). Median follow-up was 3.8 years (range: 0.1 to 13.3). When controlled for age, stage, or biomarker status, no differences in progression-free survival (PFS) were observed between the pts who underwent RSIS compared to those that did not. Conclusions: Most pts with stage III BC undergo RSIS. However, the results of RSIS infrequently affect treatment decisions. We did not observe a difference in PFS between pts who underwent RSIS and those who did not. Our findings suggest RSIS in stage III BC has limited value. A prospective study of this research question is warranted.