Introduction: Differentiated thyroid carcinoma (DTC) follow-up after thyroidectomy and radioiodine-ablation is performed mainly by thyroglobulin (Tg), diagnostic iodine-131 whole body scan (DxWBS) and sonography. Some patients with undetectable Tg have thyroid-bed uptake after ablation in whom decision making regarding the need for retreatment is still controversial. Methods: In this study, we enrolled DTC patients with undetectable Tg but small thyroid residue in six-month-DxWBS following first radioiodine-ablation. Patients with detectable Tg, high TgAb, suspicious neck lymphadenopathy in sonography and metastasis were excluded. Ninety four patients were placed in two groups of cohort, i.e., radioiodine-retreatment group (n=36) versus observation (untreated) group (n=58). After six months, the clinical outcome was compared by evaluating DxWBS, Tg, TgAb and sonography. Results: DxWBS showed sustained thyroid remnant in 47.2% of retreated patients while 34.5% of untreated group revealed negative DxWBS over the next period of follow-up. Also, only 6 cases (16.7%) in retreatment group and 12 cases (20.7%) in observation group revealed an additional finding other than local faint RAI uptake, including detectable serum Tg, rising TgAb or suspicious ultrasound finding, favoring no significant difference of the outcome as well as relative risk of new finding incidence between treated and untreated patients (CI 95% for relative risk: 0.58-2.41; p=0.630). Conclusion: Regarding sonologic and laboratory follow-up evidences, RAI-retreatment shows no significant advantage over observation in DTC patients with Tg negative, remnant positive DxWBS. In addition, residual thyroid tissue was completely disappeared in about one third of patients without retreatment.