Differentiated carcinoma of the thyroid are one of rare malignancies that is associated with excellent prognosis. Follow-up with regular thyroglobulin assay and (131)I whole-body scan is capable of detecting residual or recurrent disease with great sensitivity and specificity. However, there is overwhelming evidence to suggest that this approach is not fail-safe due to increasing reports of false negative and false positive results, which may result in missed or unwarranted therapy with (131)I. This article will review the current management of differentiated carcinoma of the thyroid and the possible causes of the reported inadequacy of thyroglobulin and (131)I whole-body scan to detect residual or recurrent disease, and the increasing role of alternative imaging, particularly (18)F-FDG PET in the management of this curable malignancy.