Thyroglobulin (Tg) and radioiodine whole body scan (WBS) have been commonly used in follow-up of patients with differentiated thyroid carcinoma (DTC). Tg is associated with radioiodine uptake in local or distant metastases. In minority of patients, the follow-up scan shows no functioning thyroid tissue, but the serum thyroglobulin is still elevated. Therefore, we review recent developments of diagnosis and treatment of those patients with differentiated thyroid cancer and with thyroglobulin elevation but negative iodine scintigraphy.