We report a case of persistent iodine-131 (131I) uptake in the thyroglossal duct region with undetectable thyroglobulin (Tg).<h4>Patient concerns</h4>A 45-year-old woman was found to have thyroid nodules on routine ultrasound, and further evaluation supported papillary thyroid carcinoma.<h4>Diagnoses</h4>After total thyroidectomy and central neck dissection, post-ablation and follow-up 131I imaging demonstrated persistent focal uptake in the midline neck. This evidence concerns the gene TG and differentiated thyroid carcinoma.