Objective To analyze the frequency and mechanisms of thymus accumulation of iodine-131 on whole body iodine-131 scan (WBS) in post-operative patients with differentiated thyroid cancer (DTC). Methods The total 547 post-treatment whole body iodine-131 scans in 276 patients with differentiated thyroid cancer were collected. The thymus accumulation of 131I on WBS was analyzed. Results The positive rate of radioiodine accumulation in mediastinum in three 131I therapy scan was 16.2%、35.5% and 20.45%, thymus uptake rate were 0%, 4.4% and 6.8% respectively in post-operative patients with DTC. Radioiodine accumulation in thymus was seen on 11 scans in 10 patients. Eight of these were second follow-up scans, three were third scans. Only one patient had persist thymus uptake on both second follow-up scan and third scan. None of these patients have evidence of metastatic disease by correlation with serum thyroglobulin and other imaging findings and clinical follow-up. Conclusion Uptake of radioiodine in the thymus on whole body iodine-131 scan in post-operative patients with differentiated thyroid cancer might be very rare and that will be the cause of a false-positive interpretation.