SUMMARY – Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.