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The whole body 131-I scan remains an important component in the postoperative treatment of patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole body scan provides a depiction of those tissues that can be ablated with therapeutic doses of 131-I. Over time, it has become obvious that the whole body scan may also reveal foci of 131-i uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-positive whole body scans in postoperative patients with thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sections; ectopic gastric mucosa; other gastrointestinal abnormalities; urinary tract abnormalities; mammary abnormalities; serous cavities and cysts; inflammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described.