Background: In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. Methods: We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. Results: Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length ( P <0.05), SUV after neoadjuvant therapy ( P <0.05), and reduction in the extent of FDG uptake ( P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. Conclusions: FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.