The present study was undertaken to evaluate the diagnostic performance of a high-sensitive thyroglobulin (Tg) immunoradiometric assay (BRAHMS Tg-S) in the follow-up of papillary and follicular thyroid cancer patients treated with total/nearly total thyreoidectomy and radioiodine ablation therapy. During TSH suppression serum Tg concentration was measured 6 weeks prior to the radioiodine ablation (onT4-Tg before ablation) as well as 3 months following treatment (onT4Tg after ablation) in 54 tumour-free and 43 metastatic TgAb-negative patients, and accurate cut-off values were calculated. The selectivity and specificity of the measurement were determined by ROC curve analysis (MedCalc statistical software). The cut-off values calculated from the serum Tg levels of onT4Tg before ablation and onT4Tg after ablation were 1.9 ng/mL and as low as 0.6 ng/mL respectively. Medical history of 894 patients (differentiated papillary n=715 and follicular thyroid carcinoma n=179) were compared with the serum levels of Tg, TgAb and TSH at regular intervals. Serum Tg concentrations of clinically tumour-free, TSH-suppressed (TSH <0.3 mIU/L) patients (N=774) treated with total/nearly total thyroidectomy was below the threshold level of the kit (<1.9 ng/mL). The sensitivity of Tg determination in TSH-suppressed thyroid cancer patients with local recurrences or lung metastases was 86% and in bone metastases was 100%. The number of false negative data (11/29) was high in patients with papillary cancer and lymph node metastases. The sensitivity of Tg determination could be increased considerably even in case of patients with lymph node metastases by excluding TgAb positive patients. Measuring of Tg and TgAb, with IRMA and RIA methods applied proved to be effective for monitoring differentiated thyroid tumours. The determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. During the follow-up of patients the most accurate cut-off value should be selected according to the applied therapy.