I-131 radioiodine scintigraphy is a well-accepted technique and used routinely in the clinical setting. Its imaging provides an excellent biologic and functional information. However, the limited physiologic biodistribution of this particular radioisotope provides minimal anatomic landmarks for precise localization. In the recent few years, integrated hybrid SPECT/CT has been introduced and used increasingly for evaluation and management of patients with well-differentiated thyroid cancer. We report two patients, a male and a female with well-differentiated thyroid cancer who had previously underwent near-total thyroidectomy and high dose I-131 treatment. Both were referred for diagnostic I-131 whole body scan because of high thyroglobulin on recent follow-up. The results of the studies revealed the male and female patients with incidental detection by SPECT of occult skull and brain parenchymal metastasis, respectively. These lesions are not detected on I-131 planar images and low resolution CT portion of SPECT/CT.