Radioiodine has aided the management of differentiated thyroid cancer for several decades. Most thyroid cancers retain the ability to trap iodine, and radionuclides of iodine can be used both diagnostically and therapeutically. The availability of sensitive diagnostic tests, coupled with the ability to deliver targeted therapy, gives physicians the ability to manage thyroid cancer better than with any other type of cancer. The correct interpretation of radioiodine scans is critical in the appropriate management of patients with thyroid cancer. False positive findings do occur. A radioiodine scan showing abnormal uptake outside the thyroid bed must be studied carefully and alternative reasons for the finding must be considered. The scan should be analysed systematically. Is there residual thyroid? If so, what is the 48 or 72 h neck uptake? Radioiodine uptake in the salivary glands, stomach, gastrointestinal and urinary tracts should be acknowledged as physiological. Diffuse uptake is seen in the liver in most patients with functioning thyroid at the time of their post-therapy scan. When there is uptake of the radioiodine outside these regions, contamination must be considered. A variety of cases illustrating true positive, true negative, and false positive findings is presented in this review, and the causes and consequences of misinterpretation of radioiodine scans are discussed.