The aim of this multicentre study was to evaluate the clinical significance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid carcinoma and to compare the results with both iodine-131 whole-body scintigraphy (WBS) and technetium-99m 2-methoxyisobutylisonitrile (MIBI) or thallium-201 chloride (Tl) scintigraphy. Whole-body PET imaging using FDG was performed in 222 patients: 134 with papillary tumours, 80 with follicular tumours and 8 with mixed-cell type tumours. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, ultrasonography, computed tomography and subsequent clinical course, to allow a comparison with functional imaging results. Sensitivity of FDG-PET was 75% and 85% for the whole patient group (n = 222) and the group with negative radioiodine scan (n = 166), respectively. Specificity was 90% in the whole patient group. Sensitivity and specificity of WBS were 50% and 99%, respectively. When the results of FDG-PET and WBS were considered in combination, tumour tissue was missed in only 7%. Sensitivity and specificity of MIBI/Tl were 53% and 92%, respectively (n = 117). We conclude that FDG-PET is a sensitive method in the follow-up of thyroid cancer which should be considered in all patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases, and particularly in those with elevated thyroglobulin values and negative WBS.