Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) is recommended as an optional study in current National Comprehensive Cancer Network (NCCN) guidelines after computerized tomography and bone scan (CTBS) in patients with stage IIA-IIIC breast cancer. We evaluated our experience with use of PET/CT in this setting prior to beginning primary systemic therapy (PST) before planned surgery. Methods: We performed medical record abstractions to identify all adult female patients with clinical stage IIA to IIIC breast cancer diagnosed at Montefiore Medical Center from January 1, 2014 to January 1, 2019 who underwent PET/CT. We calculated the proportion of patients upstaged after PET/CT, stratified by their initial clinical stages and use of PST, and examined the cost and radiation exposure associated with PET/CT compared with CTBS. Results: 227 patients with 230 breast cancers (bilateral disease in 3) met the study inclusion criteria. PET/CT was the only staging done in 195 patients (86%); 32 patients had PET/CT based on suspicious findings from prior CTBS. Among these 195 patients with 196 breast cancers (bilateral disease in 1) that had PET/CT as the only staging done, the overall upstaging rate for regional nodal and/or distant metastasis was 37% (73/196), including 24% for stage IIA (9/38), 39% for IIB (31/79), 54% for IIIA (22/41), 27% for IIIB (8/30), and 37% for IIIC (3/8). The overall upstaging rate to stage IV was 14% (27/196), including 0% for stage IIA, 13% for IIB (10/79), 22% for IIIA (9/41), 17% for IIIB (5/30), and 37% for IIIC (3/8). The sensitivity and specificity of PET/CT in detecting distant metastasis was 100% and 94%, respectively. Our institution's total Medicare reimbursement rate of PET/CT is $1604.37 whereas CTBS is $1679.94. Radiation dose for PET/CT is 14 mSv whereas CTBS is 21 mSv. Conclusions: Approximately 37% of patients with clinical stage IIA-IIIC breast cancer who underwent PET/CT prior to PST showed more extensive disease, including 23% with more extensive regional nodal metastases and 14% with distant metastasis. Given the high detection rate, comparable cost, lower radiation dose and greater convenience, PET/CT should be considered as an alternative to CTBS rather than “optional” after CTBS, especially in patients who require an efficient and expeditious work up prior to initiating PST.