During the course of tumor progression the differentiated morphologic and functional characteristics of differentiated thyroid carcinomas (DTC) disappear. This corresponds to more aggressive growth, metastatic spread, and loss of iodine uptake. Experimental data give strong evidence that differentiated functions of iodine metabolism can be reinduced by retinoic acids. Results of a study performed in patients with advanced DTC are presented. Twenty patients with DTC (eight follicular, seven papillary, five oxyphilic) were selected for treatment with retinoic acid 1.5 mg/kg body weight/day over 5 weeks. All patients had advanced tumor stages with prior operative and radioiodine treatment. Extensive tumor invasion, distant metastatic spread, or insufficient or no radioiodine uptake precluded any conventional therapeutic option. The aim was to assess the changes under retinoid treatment. Iodine uptake increased in eight patients (three follicular, three papillary, two oxyphilic). Thyroglobulin (TG) as parameter for tumor mass and differentiation increased in 12 (63%) patients, decreased in 6 (32%), and did not change in 1 (5%). Retinoids do have an effect on differentiation status of DTC, reinducing iodine uptake in 50% of patients. TG levels do not always parallel a response in iodine uptake.