Cancer-testis antigens are tumor antigens that their expression is almost limited to male germ cells in the testis. Some of cancer-testis antigens are also expressed in the ovary and in trophoblasts. Recently their expression has been seen in different types of tumors. Many pathophysiologic studies suggest that a blood-testis barrier exists in the testis. Because spermatogenesis begins at puberty, new cell-surface antigens are expressed when the immune system has refined the ability to distinguish self from nonself. So, sperms in the testis do not stimulate immune responses. In addition, although antigen-presenting cells are commonly seen in the interstitial spaces of the testis, these cells are scarcely seen within the seminiferous tubules. So, testis is considered as an immune-privileged site, and testis-specific genes, if expressed in cancers can be immunogenic. For this reason cancer-testis antigens are promising candidates for cancer immunotherapy and have become a major focus for the development of vaccine-based clinical trials in recent years. In addition, these antigens can also be used as biomarkers for early detection of cancers.