Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with an excellent prognosis. Overall survival is more than 90%. The first-line treatment is surgical excision, and although the debate continues as to whether a total thyroidectomy or thyroid lobectomy should be recommended, most patients at the University of California, San Francisco are treated with a total thyroidectomy. Not only has this been shown to be superior for overall survival in select patient populations, but local recurrence is also significantly lower with this approach. Total thyroidectomy also optimizes the adjuvant treatment options that are unique to "differentiated" thyroid cancer because these malignant cells retain many of the features of the native thyroid follicular cell. These cellular features are used for specialized investigations and treatment options in patients with PTC. For example, PTC cells retain the ability to produce thyroglobulin, to be stimulated by thyroid-stimulating hormone (TSH), and to take up iodine. These features are vital and separate differentiated thyroid cancer from other epithelial malignancies because such features can be used in clinical follow-up (monitoring serum thyroglobulin levels, whole body radioactive iodine scans) and in the treatment of patients with PTC (TSH suppression, radioactive iodine ablation of thyroid remnant, local recurrences, and regional or distant metastases). In summary, the wide array of treatment options for patients with PTC includes surgery, radioactive iodine, thyroid hormone suppression of TSH, external beam radiation (less commonly), and rarely, chemotherapy. This continues to be an area of exciting research for emerging therapy, much of which concentrates on enhancing or re-establishing the differentiated features of the thyroid cancer cell, in an effort to optimize the adjuvant treatment options. The treatment options that are chosen depend on patient factors, disease factors, and the decisions of the patient and treatment team.