In patients with differentiated thyroid cancer (DTC) total or near-total thyroidectomy, postoperative 131I ablation, and thyroid suppression therapy are reported to be associated with fewer recurrences than other treatments. Many patients with DTC after total thyroidectomy and radioablation therapy have diffuse hepatic uptake of radioiodine, and its clinical importance is debated. Some investigators report that diffuse liver uptake correlates with uptake in the thyroid bed or the presence of metastatic thyroid cancer somewhere in the body, whereas others note no such correlation. The purpose of this research was to determine the clinical importance of diffuse hepatic uptake of radioiodine after 131I ablative therapy in patients with DTC. We retrospectively reviewed 141 posttherapy scans done in 118 patients with DTC. Patients had had total thyroidectomy and were hypothyroid when serum thyroglobulin (Tg) levels were obtained, and they were treated with 30 to 200 mCi of 131I. Scans were performed 3 to 21 days after radioablation therapy. Information was collected regarding the patients' age and gender, the interval between the ablation therapy and scan, uptake of radioiodine, serum thyroglobulin level, thyroid-stimulating hormone (TSH) level, thyroglobulin antibodies, TNM classification, mortality, and recurrence. Diffuse liver uptake was classified from 0 to 4 depending on hepatic brightness. Radioiodine scans were done to determine whether there was uptake in the thyroid bed or elsewhere. Statistical analyses included analysis of variance and Kaplan-Meier survival analysis. Diffuse hepatic uptake was observed (grades 1-4) in 96.4% of the patients; thus 3.6% had no hepatic uptake. There was no significant association between liver uptake and the uptake in the thyroid bed, the dose of 131I administered for ablation therapy, thyroglobulin levels, age, stage of the disease, presence of local or distant metastases, recurrence, or survival. Diffuse hepatic uptake was therefore not associated with residual normal thyroid or metastases as suggested by some but not all previous investigators.