Thyroid cancer is the most common endocrine malignancy and its incidence goes on increasing worldwide. The majority of thyroid tumours comprise well-differentiated (papillary and follicular) thyroid carcinomas that usually carry an excellent prognosis, while a minority progress to poorly differentiated carcinoma (PDTC) and, ultimately, to the highly aggressive and lethal undifferentiated carcinoma (UTC). Recently, some major advances have been made on the histologic and imunohistochemical identification, as well as on the molecular characterization of PDTC and UTC. In this review we summarize the most recent immunohistochemical and molecular findings in PDTC and UTC, giving a particular emphasis to the diagnostic and prognostic meaning of the genetic alterations.