The incidence of differentiated thyroid carcinoma (DTC) is increasing in most developed countries. The only well-known risk factor for thyroid cancer is exposure to ionising radiation. DTC is characterised by a strong hereditability, and individual susceptibility is likely due to genetic factors modulating the environmental risk. Identification of genetic polymorphisms is important for understanding the potential mechanisms involved in thyroid carcinogenesis. In this Review, we assess epidemiological data on the role of germ-line DNA polymorphisms and the risk of DTC. We have included only case–control studies that compare the incidence of germ-line mutations in patients with DTC, with the incidence of mutations in patients without a history of DTC. Such an analysis of genetic susceptibility in differentiated thyroid cancer has not yet been published.