Melanoma antigen family A, 3 (MAGE-A3) is a cancer-testis antigen whose expression has been demonstrated in a wide array of malignancies including melanoma, brain, breast, lung and ovarian cancer. In addition, its ability to elicit spontaneous humoral and cellular immune responses has been shown in cancer patients. As antigen-specific immune responses can be stimulated by immunization with MAGE-A3, several clinical trials have used MAGE-A3 vaccines to observe clinical responses. The frequent expressions of this antigen in various tumors and its immunogenicity in cancer patients have led to application of this antigen in cancer immunotherapy. However, the results of recent clinical trials indicate that there is a need for research in the vaccine design, adjuvant selection as well as patient selection criteria.