Anaplastic thyroid carcinoma (ATC), accounting for 5% to 15% of primary malignant thyroid neoplasm, is one of the most aggressive solid tumors in humans. It is rapidly fatal, with a mean survival of 6 months after diagnosis. Multimodality treatment with surgery and/or external beam radiotherapy and chemotherapy are of fundamental importance for local control of disease and to enhance survival. Molecular biology studies have shown that ATC is associated with a p 53 mutation. ATC usually does not concentrate radioiodine or express thyroglobulin. It is essential to verify the diagnosis histologically because insular thyroid cancer, lymphomas, and medullary thyroid cancer are occasionally confused with undifferentiated neoplasms. Immunohistochemical study is helpful in establishing the diagnosis. Multimodal therapy and development of effective systemic chemotherapy agents would provide to result in improvements in survival although no single agent has yet been identified. Aggressive multimodality treatment regimens show promise in improving local control in patients with ATC. Survival rates however remain low. Despite intense applications of such integrated therapy, no standardized successful treatment protocol has yet been established.