Low risk Differentiated Thyroid Cancer (DTC) are currently rarely treated with radioiodine (131I) to ablate the postoperative remnant. Therefore, the interpretation of the serum thyroglobulin (Tg) values, should be reconsidered. The aim of our study was to evaluate the changes in Tg values during follow-up with regard to the changing values in thyroid stimulating hormone (TSH).We evaluated 271 low-risk DTC patients, treated with total thyroidectomy but not 131I. To be included, patients should be negative for Tg-antibodies and have at least 3 evaluations in our department. All patients were on levothyroxine (L-T4) therapy.After a median follow-up of 73 months the overall Tg values were stable, while TSH values were slightly increasing. Therefore, we pooled data of Tg and TSH from all evaluations and a significant positive correlation was demonstrated (R=0.2;p<0.01), also when we performed the analysis using the time-weighted values (R=0.14;p=0.02).Moreover, when dividing patients into three groups according to first postoperative Tg [Group A (Tg <0.2 ng/ml), Group B (Tg 0.2-1 ng/ml) and Group C (Tg >1 ng/ml)] most patients showed stable values of Tg at the end of follow-up but, TSH variations, had a clear impact on the changes in Tg among the groups.We demonstrated that in low-risk DTC not treated with 131I, serum Tg remains substantially stable over time and the variations observed were correlated with the concomitant variations of TSH levels, mainly due to the modification of LT-4 therapy performed according to the ongoing risk stratification.