Thyroglobulin (Tg) measurements in tissue and serum play an important role in the management of differentiated thyroid cancers. In the post thyroid ablation scenario, Tg estimation plays a very important role for detection of recurrence and metastasis. Although there could be Tg autoantibody interference in some patients, Tg is a highly specific and sensitive tumor marker for differentiated thyroid cancer in those where the autoantibody is absent. The clinical sensitivity of Tg is greatest when endogenous TSH is elevated before radioiodine imaging. Tg assays and radioiodine scans are independent indicators of residual or metastatic thyroid cancer, indicating that both these tests are complimentary. Immunohistochemical detection of Tg in surgical specimens is useful in the differential diagnosis of tumors of unknown origin. In future, measurement of Tg mRNA to detect circulating tumor cells may help to overcome some of the current limitations. Key words: Thyroglobulin Serum estimation -Antibodies mRNA testing - Differentiated thyroid cancer Radioiodine Thyroxine TSH Diagnostic use.