We evaluated the ability of dual-phase (18) F-FDG PET/CT to predict the histological response after neoadjuvant chemotherapy (NAC) in osteosarcoma. Thirty-one patients with osteosarcoma treated with NAC and surgery were prospectively enrolled. After injection of (18) F-FDG, both early (similar to 60 min) and delayed (similar to 150 min) PET were acquired before and after the completion of NAC. SUVmax, early/delayed SUVmax change (RImax), and early/delayed SUVmean change (RImean) of tumour were measured before (SUV1, RImax1, and RImean1) and after NAC (SUV2, RImax2, and RImean2). Then, we calculated the percentage changes between SUV1 and SUV2 (%SUV). Twelve patients (39 %) exhibited good histological response after NAC. SUVmax, RImax, and RImean significantly decreased after NAC. Before NAC, only RImean1 predicted good histological response with the optimal criterion of < 10 %, sensitivity of 92 %, specificity of 57 %, and accuracy of 71 %. After NAC, %SUV, SUV2, and RImax2 predicted histological response. By using combined criterion of %SUV and RImax2 or SUV2 and RImean1 or SUV2 and RImax2, accuracies were 81 %, 77 %, and 77 %, respectively. The histological response after NAC could be predicted by using RImean1 before the initiation of NAC in osteosarcoma. The combined use of SUV and RI values may provide a better prediction. aEuro cent Pretreatment dual-phase FDG-PET was useful to predict histological response in osteosarcoma. aEuro cent A combination of early and delayed PET may increase the predictive value. aEuro cent Early/delayed SUV change of tumours significantly decreased after neoadjuvant chemotherapy.