The worldwide incidence of thyroid cancer has increased and generated great debate and study concerning the proper evidence-based management strategies. Despite this increase, there has been no significant increase in advanced, invasive thyroid cancers which continue to represent the primary cause of thyroid cancer specific death. We seek to present an evidence-based management course on advanced, invasive thyroid cancer to address critical issues of diagnosis, preoperative evaluation, management of tracheal and esophageal invasion, recurrent nerve and parathyroid gland management, neck management, and adjuvant surgical procedures relating to this important subset of patients. Illustrative examples of complex patients drawn from a large single-institutional experience in which there is a very active multidisciplinary thyroid center and tumor board will be presented in the context of evidence-based literature to help guide the practitioner in an area less frequently addressed in most contemporary courses. An emphasis will be placed on the importance of the evidence-based multidisciplinary approach to optimize outcomes.