Objective To investigate the guiding value of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) coincidence circuit imaging and ¹³¹I SPECT/CT imaging on detecting metastases of differentiated thyroid carcinoma (DTC). Methods Fifty-three patients with positive findings of DTC by ¹⁸F-FDG imaging or ¹³¹I SPECT/CT imaging during ¹³¹I therapy and follow-up underwent surgical resections. The preoperative and postoperative serum human thyroglobulin (HTg) and clinical stage were observed and compared. Results Among 53 patients, 34 patients were positive on ¹⁸F-FDG imaging. DTC metastases were pathologically confirmed in 32/34 patients. Nineteen patients were positive on ¹³¹I imaging, and DTC metastases were pathologically confirmed in 17/19 patients. In 49 patients with true positive DTC metastases on radionuclide imaging, 38 patients had positive serum HTg before surgery. HTg remained positive in 23/38 patients. There was significant difference of HTg before and after surgery (P<0.05). ¹⁸F-FDG and 131I imaging guided surgery changed the clinical stage for 11/32 and 3/17 patients, respectively. Conclusion ¹⁸F-FDG and ¹³¹I imaging were sensitive to detect DTC metastases.