The quantitative relationship between iodine and glucose metabolism in metastases from differentiated thyroid cancer (DTC) remains unknown. Aim of the prospective study was to establish the value of 18F-FDG PET/CT in predicting 131I-avidity of metastases from DTC before the first radioiodine therapy. A total of 121 postoperative DTC patients with elevated stimulated serum thyroglobulin (ssTg) who underwent 131I adjuvant therapy or therapy after 18F-FDG PET/CT scan were enrolled. The Receiver operating characteristic curve was established to create an optimal cut-off point and evaluate the value of SUVmax for predicting 131I-avidity. In our study, the median SUVmax in 131I-nonavid metastatic target lesions was also significantly higher than that in 131I-avid metastatic target lesions (5.37 vs. 3.30; P = 0.000). At a cut-off value of 4.0 in SUVmax, the area under curve was 0.62 with the sensitivity, specificity, positive predictive value and negative predictive value of 75.3%, 56.7%, 76.1%, and 54.8%, respectively. These results suggest that 18F-FDG PET/CT may be of great value in identifying metastases in postoperative DTC patients with elevated ssTg before 131I administration, leading to an improved management of disease. 18F-FDG positive metastatic DTC with SUVmax of greater than 4.0 possesses higher probability of non-avidity to radioiodine.