Anaplastic thyroid carcinoma may represent the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the poorest cancers in human. It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade. Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently. Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemical study can be necessary to exclude lymphoma and to validate aggressive therapies. Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy. Therapeutic researches investigate redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in elderly.