Differentiated thyroid cancer of follicular cell origin (DTC) is a fascinating tumor because of its varying aggressiveness. Luckily most patients with these cancers, despite regional metastasis, can be cured by surgical resection, radioiodine ablation and thyrotropin (TSH) suppression therapy. Unfortunately some patients with well differentiated thyroid cancer that fail to respond to conventional treatment and also patients with poorly differentiated thyroid cancers or anaplastic thyroid cancers are not successfully treated by this combined therapy. These tumors unfortunately may grow rapidly, invade adjacent structures and spread to other parts of the body. During the dedifferentiation process, these carcinomas lose thyroid specific gene expressions including the ability to take up and organify radioiodine and to make thyroglobulin (Tg). The methods used to treat patients with DTC are therefore usually not effective in these patients. These tumors also usually fail to respond to alternative treatment with external radiation or systemic cancer chemotherapy. We therefore need to develop new treatments for these unfortunate patients. Recent advances in molecular and cellular biology make it possible to develop new therapeutic approaches to thyroid cancer. Genes related with thyroid specific functions are also promising targets for cancer therapy. Redifferentiation therapy targets thyroid specific genes in order to restore thyroid specific differentiated function and thus to make these tumors respond to conventional therapy. Redifferentiating agents and gene therapy using thyroid specific genes have been studied for this purpose. Most of therapeutic approaches described here have been established effects in vitro but have not yet been used clinically. Careful clinical trials and analyses should be performed.