Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive tumor characterized by rapid growth that causes death soon after diagnosis. Optimal treatment is debatable because of inherent difficulties investigating a rare malignancy associated with a survival of only months. Nevertheless, there is evidence that a multimodality approach consisting of surgery, chemotherapy, and radiotherapy is the preferred approach when the disease is localized. Eradication by complete surgical resection with total thyroidectomy, although often not feasible, followed or preceded by concurrent doxorubicin-based chemotherapy and hyperfractionated external beam radiation has been occasionally used and can rarely be associated with long-term survival. Surgical extirpation with radical organ resection is associated with high morbidity, and, although an aggressive surgical approach is reasonable in selected patients, organ preservation should be the goal in a disease with high recurrence and death rates. Any modality used in isolation usually fails to control local and regional ATC. In otherwise healthy patients who can tolerate aggressive therapy, chemoradiation and surgery may also be warranted for palliating incurable disease in the neck, which can cause death by asphyxiation.