Recently, the main therapy of medullary thyroid cancer (MTC) is surgical, but by which way there is a poorprognosis with a mean survival of only 5 years. In some cases, some researchers found that it is the medullarythyroid cancer stem cells (MTCSCs) that cause metastasis and recurrence. This study aimed to eradicate MTCSCsthrough administration of all-trans-retinoic acid (ATRA). Here we demonstrate that MTCSCs possess stemlikeproperties in serum-free medium. The ABCG2, OCT4 and sodium iodide symporter (NIS) were changedby ATRA. Additionally, we found that ATRA can increase the expression of NIS in vivo. All the data suggestedthat ATRA could increase the iodine uptake of MTCSCs through NIS.