This course is a case-based panel discussion with thyroid cancer experts which aims to highlight the updates and advances of recent years regarding treatment options of advanced thyroid cancer and the role that molecular mutations have in targeted therapies and multimodality strategies. Advanced thyroid cancer is often encountered by otolaryngologists specializing in head and neck surgical oncology and occasionally by comprehensive otolaryngologists in the private practice setting. Management of patients with advanced thyroid cancer can present multiple challenges including decisions about extent of surgical intervention as well as the order and timing of adjuvant therapies. Complicating the issue further, over the past 5 years, we have seen the development and approval of multiple new chemotherapeutic and immunotherapeutic agents with the potential to radically change our treatment algorithms for certain patients. Many of these drugs are still in clinical trials but given the possibility of substantial clinical benefit for select patients, it is important that there is general knowledge of these options. The first goal of this session is to define advanced thyroid cancer and identify the diagnostic studies that are indicated to confirm advanced disease. The second goal is to discuss the specific molecular mutations and profiles that can be identified in advanced thyroid cancer and the targeted and non-targeted treatment options that are available depending on the results of molecular testing. Finally, the session will discuss and debate aspects of surgical decision making, appropriate surgical aggressiveness, and the role of adjuvant therapies and clinical trials. The session will use case presentations to illustrate state-of-the-art management of patients with advanced thyroid cancer.