Inclusion Criteria:

The study population will consist of men and women with histologically confirmed stage 2 (younger than 45 years of age), 3 or stage 4 differentiated thyroid cancer (e.g., papillary or follicular thyroid cancer) that has been previously treated with at least one course of radioactive iodine therapy and has evidence of residual, recurrent or progressive disease documented by any combination of radiologic studies and thyroglobulin levels.

To be eligible for inclusion, patients must fulfill each of the following criteria:

1. Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
2. Age >18 years.

3. Histologically confirmed stage 2 (younger than 45 years of age), 3 or stage 4 differentiated thyroid cancer (i.e., papillary or follicular thyroid cancer).

   a. If a patient has distant metastases, it must be documented by any combination of radiographic studies or whole body radioiodine scanning.

4. Previously treated with at least one course of radioactive iodine (I-131) therapy.
5. At least one measurable site of disease as defined by the Tumor Assessment Criteria in Appendix 3.

6. Serum thyroglobulin levels inappropriately elevated:

   > 60 ng/mL with thyroid gland > 1 ng/mL without thyroid gland

7. ECOG performance status 0-2.
8. Life expectancy ≥ 3 months.

9. Normal organ function. The definitions of minimum adequacy for organ function required prior to study entry are as follows:

   1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 x upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy.
   2. Total serum bilirubin less than or equal to 1.5 x ULN.
   3. Serum albumin greater than or equal to 3.0 g/dL.
   4. Absolute neutrophil count (ANC) greater than or equal to 1500/uL.
   5. Platelets greater than or equal to 100,000/uL.
   6. Hemoglobin greater than or equal to 9.0 g/dL
   7. Serum creatinine less than or equal to 1.5 x ULN.
10. Agreement to use contraceptives for women with child bearing potential. Unless surgically sterile, men must agree to use effective contraception during period of therapy.
11. The patient must be aware of the nature of his or her malignancy, understand the protocol requirements, risks, discomforts, and be able and willing to sign an informed consent.

Exclusion Criteria:

Patients who fulfill any of the following criteria will be excluded:

1. Prior systemic chemotherapy or targeted therapy within 3 months prior to enrollment.
2. Prior treatment on a Sutent clinical trial or current treatment on another clinical trial.
3. Prior external beam radiation therapy to the target lesion(s).
4. Life expectancy < 3 months.
5. History of any other carcinomas within the last 5 years, except cured basal cell carcinoma of the skin and cured in-situ cervical cancer.
6. Serious uncontrolled concomitant disease that the Investigator feels might compromise study participation.
7. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, or the inability to take oral medication.
8. Any of the following clinical conditions within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, pulmonary embolism, ongoing cardiac dysrhythmias of NCI CTCAE grade at least 2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females.
9. Uncontrollable hypertension.
10. Known human immunodeficiency virus infection.
11. Current treatment with therapeutic doses of Coumadin-derivative anticoagulants (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
12. Patients with a history of uncontrolled seizures, central nervous system disorders of psychiatric disability judged by the Investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake should be excluded from study.
13. Inability to swallow whole tablets.
14. Unwillingness to participate or inability to comply with the protocol for the duration of the study.