Thyroid tumors are the most common endocrine malignancy. The main genetic changes are point mutations in the RET proto-oncogene (somatic or germ-line) in medullary thyroid carcinoma and point mutations in BRAF and RAS genes or RET/PTC rearrangements in carcinomas developing from follicular cells. Moleculargenetic diagnosis of RET mutations in patients with medullary thyroid carcinoma and their relatives is now the part of clinical approach. Currently, knowledge about genetic causes of thyroid tumors has begun applying into target gene therapy providing new therapeutic drugs and more individualized treatment. This review summarizes main genetic causes of thyroid tumors and their application in target gene therapy.