Measurement of serum thyroglobulin (Tg) is a highly specific test in the management of patients with differentiated thyroid cancer (DTC) after surgical treatment. The aim of our study was to evaluate and compare Tg levels in these patients found by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) and to assess the influence of Tg antibodies (TgAbs) on the values obtained for Tg concentration. Both Tg and TgAb were determined postoperatively in the serum of 71 DTC patients using RIA Tg-PEG (INEP) and Tg IRMA (CIS) for Tg, together with TgAb (CIS) for circulating endogenous anti-TgAbs. The obtained concentrations were evaluated statistically. We found a significant difference of Tg concentrations between paired samples from the IRMA and RIA, although the intermethod comparison yielded satisfactory concordance of the two assays (Spearman correlation coefficient -0.792). Positive TgAb was found in 28.2% of the serum samples analyzed. Spearman rank correlation analysis revealed a significant negative relationship between serum TgAb and Tg level measured by IRMA (P=0.02), but not by RIA (P=0.417). On the other hand, our clinical data revealed that 1/18 and 3/18 patients with proven lymph node metastasis had Tg values below the detection limit by RIA and IRMA assay, respectively. Their sera were TgAb positive. We concluded that RIA was less prone to influence of TgAb than IRMA. As the presence of TgAbs may interfere in Tg measurement irrespective of the method selected for determination, this should be considered during the clinical management of these patients.