Iodine-131 (I-131) treatment and subsequent whole body iodine-131 scans (WBSs) are important in the management of differentiated thyroid carcinoma (DTC). Nevertheless, false positive benign lesions in WBS should be interpreted with reliable anatomic imaging methodologies to differentiate from true metastases. We report a DTC case with a concurrent thyroglossal duct cyst (TDC), which is relatively uncommon compared with an accompanying lingual thyroid. After thyroid remnant ablation, subsequent posttherapeutic WBS showed a stable I-131 avid lesion in the neck despite cumulative dosage of 346 mCi I-131. Low level of thyroglobulin indicated that the lesion should be from thyroid origin, yet only a small amount of thyroid remnant should be contained. Magnetic resonance imaging and computed tomography were performed and revealed a dumbbell-shaped TDC. Part of the lesion was behind the hyoid bone, part of it protruded to the anterior surface of the thyroid cartilage, and the isthmus penetrated through the thyrohyoid membrane. Although the shape of this TDC reflects the route of the thyroglossal duct in embryological perspective, its coincidence with DTC is rarely documented. Our case also proved that the possibility of concurrent TDC should be considered as the cause of residual thyroglobulin for an I-131 avid lesion in the midline anterior cervical area, which could show great resistance to I-131 therapy.