PurposeIn pediatric patients with differentiated thyroid cancer (DTC) we assessed the prognostic value of the 12-month response to therapy after initial treatment with surgery and radioactive iodine (RAI).MethodsWe retrospectively evaluated 94 pediatric patients with DTC, treated with surgery and RAI who were initially classified as low, intermediate or high risk of relapse of disease according to the American Thyroid Association (ATA) guidelines. Twelve months after RAI administration the response to therapy was assessed by serum thyroglobulin (Tg) measurement and neck ultrasound and patients were classified as having excellent response (ER) or no-ER.ResultsAt the 12 months evaluation, 62 (66%) patients had ER and 32 (34%) no-ER. During a mean follow-up time of 86 months (range 9–517), 19 events occurred (20% cumulative event rate). Events occurred more frequently in younger patients (p< 0.05), in those at ATA intermediate/high risk (p< 0.01) and with a pre-RAI therapy Tg level > 10 ng/mL (p< 0.001), and in those with no-ER (p< 0.001). At multivariate analysis, the evidence of no-ER was the only independent predictor of events.ConclusionIn pediatric patients with DTC, the response to therapy evaluated 12 months after initial treatment has an independent prognostic impact and is able to predict mid-term outcome. Patients with no-ER at 12 months after RAI therapy should be closely followed-up.