Background: This study aims to demonstrate the superiority of Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) over planar imaging in distinguishing benign from malignant foci and patient management after 131I ablation therapy in patients with differentiated thyroid cancer (DTC). Material and Methods: Planar and SPECT-CT imaging findings were retrospectively analyzed in Eighty patients who received I-131 therapy for thyroid cancer. Possible foci in whole body scanning (WBS), neck, and thorax were compared with SPECT-CT. Anatomical localization of the foci and differential diagnosis of the benign and malignant lesion was made with SPECT-CT. Those without anatomical counterparts were recorded as equivocal foci. According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into three groups: High, intermediate, and low-risk groups. Interpretation changes between both scannings were recorded as downstage and upstage. Results: A total of 80 patients, 53 female, and 27 male, were included in the study. The patients’ age ranged from 21 to 88 years with a mean age of 47 ±14.2. In 80 patients, 139 foci were detected in planar images and SPECT-CT images (neck: 118, thorax: 21). SPECT-CT revealed that 50% of the lateral neck foci were compatible with pathologies of malignant nature and 50% with pathologies of benign nature. Foci in the middle part of the neck were not only thyroid remnant (56%) but also thyroglossal duct remnant (40%) foci at a significant rate. It was determined that 66% of the foci in the thorax region were lung metastases,and 34% were bone metastases. It was proved that 33% of the foci in the mediastinal area were lymph nodes. Although only one of the remaining patients had a pathological diagnosis, it was thought that all of them might have thymus pathologies. SPECT-CT images changed the interpretation of 18 patients (22.5%), 5 of whom (6.25%) were upstage and 13 (16.25%) were downstage. Conclusions: SPECT-CT will be very effective in, facilitating patient management and avoiding unnecessary procedures, especially in moderate/high-risk patients with suspicious focal lesions. Knowing the benign iodine uptake foci (thyroglossal duct remnant, etc.) that show iodine uptake other than the thyroid residue in the neck may be influential in deciding whether to ablate in low-risk patients.