Anaplastic (undifferentiated) thyroid carcinoma is the least common form of primary thyroid carcinoma, with an incidence rate of 0.21 per 100,000 person years in the United States [1], and accounting for approximately 2% of all thyroid malignancy [2]. Worldwide, the incidence of anaplastic carcinoma varies regionally from 1% to as high as 26% of thyroid carcinoma [3]. Geographic variations in incidence are thought to be related to dietary iodine intake, as well as detection and management of precursor lesions (differentiated thyroid carcinomas) [2, 4]. Although uncommon, anaplastic thyroid carcinoma is disproportionately fatal compared with differentiated forms of thyroid carcinoma and causes more than 50% of thyroid carcinoma-related deaths [4]. This chapter reviews the clinicopathologic features of anaplastic thyroid carcinoma, as well as the current state of knowledge as to the molecular underpinning of disease, and discusses current and emerging therapeutic options.