Background: Neoadjuvant chemotherapy (NAC) is a therapeutic option for locally advanced breast cancer and is aiming to reduce tumor volume for breast conservation. Accurate assessment of residual tumor after NAC is a crucial for determining the outcome and survival of the patients. Eighteen fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) has been recently used as a reliable tool to evaluate response to treatment due to combined morphologic and metabolic information. The aim of this study was to assess the value of 18 F-FDG PET/CT in evaluation of response to NAC in a sample size of recently diagnosed 30 locally advanced breast cancer patients, who were referred for 18 F-FDG PET/CT scanning before and after NAC. The morphologic and metabolic response was evaluated and compared to histopathologic findings. Results: 18 F-FDG PET/CT detected 23 responders and 7 non-responders among the examined 30 breast cancer patients, compared to 20 responders and 10 non-responders detected by CT alone. 18 F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 95.5%, 75%, 91.3, 85.7, and 90%, respectively, compared to 81.8%, 75%, 90, 60, and 80%, respectively, achieved by CT alone. Conclusion: 18 F-FDG PET/CT is a reliable single whole body imaging tool which can be used in monitoring of NAC response in patients with locally advanced breast cancer showing higher sensitivity and accuracy compared to CT alone.