Background and Objective: I-124 emits a positron and can be imaged with a positron emission tomography (PET) scanner. The objective of this study was to compare the ability of diagnostic 124 I PET images versus I-131 planar whole-body imaging in detecting residual thyroid tissue and/or metastatic well-differentiated thyroid cancer (WDTC). Methods: Patients were recruited prospectively for this study who (i) had WDTC, (ii) were suspected of having metastatic WDTC, and (iii) were referred for I-131 whole-body dosimetry. The prescribed activity was 1-2 mCi (37-74 MBq) and 1.7 mCi (62.9MBq) for I-131 and I-124, respectively. For each image, one blinded reader (D.V.N.) categorized every focus of I-131 and I-124 radioiodine uptake as 1 definite physiological uptake/artifact, 2 most likely physiological uptake/artifact, 3 indeterminate, 4 residual thyroid tissue/metastases in the neck/ bed, 5 most likely metastases, or 6 definite metastases. Foci categorized as 4, 5, or 6 were considered positive. When available, foci categorized as 4, 5, or 6 were correlated with other diagnostic studies. Results: Of the 25 patients, 8 patients (32%) had more positive foci on I-124 images than on I-131, of which 3 patients to date have had metastases confirmed in one or more of the additional positive I-124 foci. I-124 demonstrated the same number of foci as on I-131 in 16 patients (14 with no positive foci, and 2 with two positive and five positive foci each). One patient had one additional positive focus on I-131 not seen on I-124, which has not yet been confirmed as a metastasis. A total of 97 positive foci were identified on either I-124 or I-131. I-124 identified 49 positive foci not seen with I-131, and I-131 identified one positive focus not seen with I-124. Conclusion: Relative to I-131 planar whole-body imaging, I-124 PET identified as many as 50% more foci of radioiodine uptake suggestive of additional residual thyroid tissue and/or metastases in as many as 32% more patients who had WDTC.