Carcinomas of the thyroid comprise a heterogeneous group of neoplasms with distinctive clinical and pathological characteristics. Over the past 15 years, the application of molecular technologies to the study of these neoplasms has elucidated critical genetic pathways associated with the development of specific thyroid tumor types. In papillary thyroid carcinoma (PTC), genetic events involve RET and TRK (rearrangements) and BRAF and RAS (mutations), although RAS mutations are uncommon except in the follicular variant of PTC. These genetic alterations, which rarely overlap in the same tumor, result in signaling abnormalities in the mitogen-activated protein kinase pathway. In contrast, genetic alterations in follicular carcinomas include PAX8-PPARgamma translocations and RAS mutations while mutations of CTNNB1 and p53 have been implicated in the development and progression of poorly differentiated and undifferentiated (anaplastic) thyroid carcinomas. Germline mutations of RET are responsible for the development of heritable forms of medullary thyroid carcinoma (MTC) while somatic mutations of this oncogene are found in a significant proportion of sporadic MTCs. The results of these studies not only have provided additional approaches to thyroid tumor classification, but also have stimulated the development of novel approaches to tumor diagnosis and additional parameters for prognostic assessment and potential biologic therapeutic strategies.