Autonomously functioning thyroid nodule (AFTN) includes a wide spectrum of unique or multifocal diseases, either hyper or euthyroid, which share the same independence from thyroid stimulating hormone (TSH) regulation in terms of growth and function. The pathological basis and the recent molecular implications of the disease are briefly discussed. Clinical and epidemiologic data of 1572 patients with AFTN, out of a population of 14107 patients with thyroid diseases, sequentially evaluated from 1974 to 1992, have been retrospectively examined. The mean age of AFTN occurrence is 41 years and it appears more frequently in women (F/M = 5.3/1). Clinical hyperthyroidism occurs only in 17% of patients and is more frequently observed in men over 40 years of age. The presence of sonolucent area inside the nodule is detectable in 8.6% of cases and may be associated with spontaneous arrest of growth. When AFTN is submitted to cytologic evaluation, patterns similar to those observed in nodular goiter are shown (colloid lesion, cyst and nodular hyperplasia). Signs of hyperactivity are also shown by follicular cells. In the presence of a cyst, a fine needle aspiration was performed and a complete resolution was observed in 40% of cases. When cyst recurred after aspiration, a solution of tetracycline was inserted into the cavity. Sclerosing therapy was efficient in evacuating the volume of the nodule in 50% of the cases. Patients with AFTN were followed for a mean period of 61 months and 84.7% of them did not show any morphological or functional change, while the remaining 15.3% of cases became hyperthyroid.(ABSTRACT TRUNCATED AT 250 WORDS)