Four types of thyroid cancer comprise more than 98% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) may have a very benign course while undifferentiated thyroid carcinoma (UTC) belongs to the most aggressive human malignancies. A variety of genes have been identified to be involved in the pathogenesis of thyroid carcinoma. Somatic Ras mutations seem to be an early event and are frequently found in follicular thyroid carcinomas. Somatic rearrangements of RET and TRK are almost exclusively found in PTC and may be found in early stages. Germline RET missense mutations lead to hereditary medullary thyroid carcinoma (MTC). In contrast, the significance of somatic RET mutations in sporadic MTC is unknown. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma. The precise role of PTEN remains to be elucidated. The only clearly identified exogenous factor that may lead to thyroid carcinoma (mainly PTC) is radiation. Of interest, radiation is capable to induce RET rearrangements. In general, early diagnosis is mandatory to enable the chance of cure. Surgery is the treatment of choice. Depending on the tumour type, surgery in combination with either radioiodine, external radiation or chemotherapy often enables the control of local tumour burden. In MTC and UTC, once thyroid cancer is spread to distant organs, efficacious therapeutic agents are almost non-existing. However, our growing knowledge of genes involved in thyroidal oncogenesis may contribute to the development of more effective treatment modalities. Some preliminary data on gene therapy are quite promising.