Well-differentiated thyroid cancer is the most common endocrine malignancy with an increasing incidence. Most patients with well-differentiated thyroid caner have a favorable prognosis with high survival rate. While surgery and radioiodine therapy is sufficient treatment for the majority of patients with differentiated thyroid cancer, a minority of these patients experiences progressive, life-threatening growth and metastatic spread of the disease. Because there is no prospective controlled study to evaluate the differences of management of thyroid cancer, it is hard to choose the best treatment option. And there are still lots of controversies about the management of this disease, such as surgical extent, proper use of radioiodine for remnant ablation and therapy, use of rhTSH instead of withdrawal of thyroid hormone, long-term follow-up strategy, thyroglobulin as a tumor marker, etc. In this review, recent data related to these conflicting issues and recent advances in diagnosis, radioiodine therapy and long-term monitoring of well-differentiated thyroid cancer are summarized. (Nucl Med Mol Imaging 2006;40(2):132-140)