Abstract: Tg (thyroglobulin) is an established serum tumour marker in the follow-up of differentiated thyroid cancer. However, serum Tg measurement remains one of the most difficult biochemical tests for a laboratory to maintain to a high level of precision and reliability. TgAb (Tg antibody) interference is the most serious specificity problem affecting serum Tg measurement, regardless of the assay. This review presented an overview of the critical problems that should he taken into account in the measurements and clinical evaluation of serum Tg and TgAb in differentiated thyroid cancer.