Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a restricted expression patternin normal gametogenic tissues but expression in a broad range of malignancies. Their expression pattern hasmade them potential targets for immunotherapy. However, expression of some of these antigens has beendemonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs have been shown to be sourcesof metastasis and tumor recurrence, novel therapies are being focused on their eradication. On the other hand,CTA expression in normal stem cells raises the possibility that CTA based immunotherapies cause side effectsin normal tissues.