Non-small-cell lung cancer (NSCLC) and melanoma are devastating diseases with high rates of recurrence. Current clinical recommendations include postoperative adjuvant chemotherapy in stages II and IIIA NSCLC, while there is a debate regarding its clinical benefit in stage IB. Recent Phase II trials have demonstrated a clinical benefit by postoperative vaccine with melanoma-specific antigen A3 (MAGE A3) in NSCLC and in stage IV melanoma. These trials have led to the current Phase III trials. MAGE A3 is a tumor-specific shared antigen that is frequently expressed in lung cancer and melanoma, as well as in few other tumors. Its level is associated with disease burden and with prognosis, while normal tissues do not express it, except the testis and the placenta. This review will summarize the recent developments and clinical experience with the MAGE A3 vaccine.