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The purpose of the study was to determine the diagnostic impact of 131I-SPECT/CT imaging compared with conventional scintigraphic evaluation in the follow-up of patients with thyroid carcinoma. Seventy-one patients with thyroid carcinoma underwent concurrent 131I-SPECT/CT, using an integrated imaging system, at various stages of their disease in order to evaluate foci of uptake detected on planar whole-body images. SPECT/CT imaging had an incremental diagnostic value in 57% (41/71) of patients. Uptake in the neck was evaluated in 61 patients, and SPECT/CT imaging in this region had an incremental diagnostic value in 27% of the whole patient population (19/71). Low-resolution integrated CT images allowed for the precise characterization of equivocal neck lesions on planar imaging in 14/17 patients and changed the assessment of the lesion location in five patients as compared with planar studies. Thirty-six patients underwent SPECT/CT for evaluation of foci of uptake distant from the neck. SPECT/CT imaging improved characterization of equivocal foci of uptake as definitely benign in 13% (9/71) of patients. Precise localization of malignant lesions to the skeleton was possible in 17% (12/71) and to the lungs versus the mediastinum in 6% (5/71) of patients. Integrated 131I-SPECT/CT was found to have an additional value over planar imaging in patients with thyroid cancer for correct characterization of equivocal tracer uptake seen on planar imaging as well as for precise localization of malignant lesions in the neck, chest, and skeleton. SPECT/CT optimized the localization of 131I uptake to lymph node metastases versus remnant thyroid tissue, to lung versus mediastinal metastases, and to the skeleton. It also had a further clinical impact on patient management by influencing referral for 131I treatment, tailoring of the administered radioiodine dose, and/or the addition of surgery or external radiation therapy when indicated.