Once undifferentiated thyroid cancer is confirmed, the patient should be immediately staged, the airway should be evaluated by fiberoptic laryngoscopy, and a treatment plan should be rapidly developed and implemented. The primary lesion needs to be evaluated to determine whether it needs to be resected, and patients who need to be resected should be treated with external radiotherapy immediately after resection, preferably with radiotherapy-sensitive agents such as paclitaxel, combined with platinum or aminoglutethimide. Palliative radiotherapy is often recommended for patients in whom the primary lesion cannot be resected and no distant metastases are found. Management of patients with advanced disease with distant metastases is more challenging. Physicians need to weigh the pros and cons between controlling the primary tumor and metastases. Those with prominent primary lesions should be treated with radiotherapy first. Patients with stable airway conditions can receive systemic chemotherapy with cytotoxic agents and are recommended to join clinical trials. Targeted therapies are the latest research findings. For example, BRAF inhibitors are used in the treatment of undifferentiated thyroid cancer with BRAFV600E mutation. A clinical trial of the selective BRAF inhibitor dabrafenib and the MEK inhibitor trametinib showed progressive patient improvement. A variety of approaches, including immunotherapy, are under study, and immunotherapy usually induces degeneration of the mass several months after initiation, making it inappropriate for those patients who need a rapid onset of action. Patients and family members should be aware of the poor prognosis of this disease, as well as the needs and desires of the patient. Hospice care is recommended for patients who do present clinically poorly or who have no treatment complaints.