Controversies in treatment of thyroid cancer remain despite numerous published studies. Robust comparative effectiveness studies examining: (1) the role of prophylactic central compartment neck dissection (pCCND) in patients with papillary thyroid cancer (PTC); (2) the use of post-operative radioactive iodine (RAI) ablation therapy following total thyroidectomy; (3) use of low versus high doses of I-131 in RAI therapy; (4) thyroid hormone withdrawal (THW) versus recombinant thyroid stimulating hormone (rhTSH) prior to RAI; and (5) the role of routine measurement of serum calcitonin levels are needed to help strengthen existing treatment recommendations. Reasons for the controversies and suggestions for quality comparative effectiveness studies are discussed.