Thyroglobulin (TG) immunohistochemistry on formalin-fixed, paraffin-embedded thyroid tissue is a functional morphological method to analyse qualitatively and quantitatively benign and malignant lesions of the thyroid. In this article new aspects of pathogenesis, functional morphology and differential diagnosis resulting from the application of this method are reported. According to our immunohistochemical and electron microscopic findings the formal pathogenesis of nontoxic (sporadic) goitre is characterized by the progressive transformation of active small thyroid follicles into inactive macrofollicles. In nodular goitre, the final stage of this process, the macrofollicles are probably irreversibly inactive and not TSH-responsive. Thyroid adenomas can be divided scintigraphically and by TG immunohistochemistry into endocrine active ("hot") and endocrine non-active ("cold") adenomas. The first group consists of autonomous adenomas, second group of other maincell adenomas and adenomas of specific cytological differentiation (e.g. oxyphilic and clear cell adenomas). In metastasizing differentiated thyroid carcinomas TG immunohistochemistry is a reliable method to differentiate primary thyroid carcinomas from other adenocarcinomas, e.g. lymph node metastases of the neck in the case of papillary carcinomas or bone metastases in cases of follicular carcinomas of the thyroid.