Background and aims: Patients' response to treatment in differentiated thyroid cancer (DTC) is classified ac-cording to serum thyroglobulin concentrations (Tg), usually using the American Thyroid Association guidelines and considering potential interfering anti-thyroglobulin antibodies (Ab-Tg). We aim to evaluate the clinical implications of changing Tg and Ab-Tg quantification method. Material and methods: Tg and Ab-Tg were quantified in 82 serum samples (60 from DTC patients) by Elecsys and Access immunoassays. Results: Elecsys immunoassay rendered higher values of Tg than Access: mean bias 5.03 ng/mL (95%CI:-14.14-24.21). In DTC patients, there was an almost perfect agreement for response classification (kappa index = 0.833). Discrepancies appeared in patients with undetermined response, with a more tendency to subclassifi-cation with Access. Ab-Tg showed a poor correlation (r = 0.5394). When Elecsys cut-off was reduced to 43 IU/ mL, agreement for positive/negative classification improved from a kappa index of 0.607 to 0.650. Prospective study with personalized follow-up showed that only 6.3% of Tg results required an analytical confirmation, being confirmed 93% of them. Conclusions: Despite the biases observed, clinical impact of an analytical change is minimal in patients' man-agement. However, cautious and personalized follow-up period after the change is still mandatory, especially in patients with Tg levels between 0.2 and 1 ng/mL.