Differentiated thyroid cancer is a rare disease and until recently was considered to be sporadic. However, increasing evidence has been found for a genetic basis of this disease. In approximately 5% of patients the differentiated thyroid cancer is dominantly inherited. Several families with different syndromes, of which differentiated thyroid cancer is a feature, have already been described. However, until now, single genes explain only a minority of cases. We hypothesize that differentiated thyroid cancer is a polygenic disease. Data from epidemiologic studies, about occult and multifocal carcinomas and the different response to specific risk factors contribute to this hypothesis.