The ability of thyroid cancer to incorporate radioiodine and to produce thyroglobulin (Tg) is an important tool for the diagnosis of tumor relapse. However, some patients show high serum Tg and negative whole body scan (WBS) since some specific thyroid properties may be lost during tumor progression. In these cases, a more careful diagnostic approach is necessary. Here, we report the case of a patient with undetectable serum Tg under levothyroxine (L-T4)-suppressive therapy and with a negative WBS 3 years after apparent thyroid remnant ablation. After detection of Tg mRNA in peripheral blood, the patient was re-investigated, and no suspicious lesions were detected by diagnostic WBS, neck ultrasonography, or thorax computerized tomography, except an elevation of serum Tg during hypothyroidism. Since retinoic acid (RA) is being used for the induction of radioiodine uptake by tumors expressing their receptors, we aimed to reveal the site of thyroid cancer relapse in this patient by isotretinoin administration. We demonstrate that apart from being a therapeutic option in some patients with thyroid cancer, RA can also be able to localize thyroid tissue in patients with high serum Tg and negative WBS.