Little progress has been made in advancing the treatment of locally advanced thyroid cancer. Patient identification, evaluation and proper surgical management with adjuvant therapy, still remain the most effective course of treatment. Aggressive surgical treatment including removal of all gross tumor and still preserving vital structures along with adjuvant therapy is likely to offer the best results. There is a very high incidence of locoregional and distant failure in this group of patients. The understanding and recognition of histopathological variations, such as poorly differentiated thyroid cancer is also important. New molecular markers are needed to help identify and predict aggressive tumor behavior.