PURPOSE: To compare the sensitivity of I-123 total body iodine (TBI) scan, I-131 TBI, and PET scanning with 2-deoxy-2[F-18]fluoro-D-glucose (FDG-PET) scans for detection of residual/recurrent disease in patients with diffuse sclerosing variant of papillary thyroid cancer. MATERIALS: A 45-year-old woman with status post-thyroidectomy and modified neck dissection showed papillary thyroid carcinoma with a diffuse sclerosing variant and positive lymph nodes. Six weeks after surgery, I-131 TBI and FDG-PET scans showed no residual or metastatic disease. However, clinical suspicion for disease remained, and an I-123 TBI scan was performed. RESULTS: I-123 TBI showed a tiny residual focus in the left thyroid bed. The patient was treated with 150 mCi oral I-131 sodium iodide; posttreatment scan confirmed the presence of residual disease. Follow-up I-123 TBI scans up to 2 1/2 years posttreatment were negative. CONCLUSION: Total body imaging with I-123 was more sensitive than I-131 TBI scanning for detecting residual or recurrent disease in patients with well-differentiated thyroid cancer presenting with low preoperative thyroglobulin levels.