Cancer-testis (CT) antigens were identified as a group of highly attractive targets for cancer immunotherapy because of their expression in a variety of malignant tumors but solely in the testis among the normal adult tissues. To evaluate the potential of two members of this family, MAGE-A4 and NY-ESO-1 antigens, for cancer vaccine in non-small cell lung carcinoma (NSCLC), we examined the expression of these antigens and T cell infiltration in tumor tissue, and evaluated their prognostic significance. One hundred fifty-seven patients with NSCLC were studied. Reverse transcription-PCR was performed to evaluate MAGE-A4 and NY-ESO-1 expression. Immunohistochemistry was performed for NY-ESO-1 expression and T cell infiltration into the tumor site. Survival analysis was also performed. MAGE-A4 and NY-ESO-1 were expressed in 40 of 141 (28.4%) and 13 of 157 (8.3%) NSCLC respectively. Both CT antigens were more frequently expressed in squamous cell carcinoma (SCC) than in adenocarcinoma. An inverse correlation was found between MAGE-A4 expression and patient survival in advanced stage cancers. Combined infiltration of both CD4+ and CD8+ T cells into tumor nest predicted better survival. There was no correlation, however, between lymphocyte infiltration and antigen expression in the tumor. MAGE-A4 expression in advanced group and T cell infiltration may provide prognostic information. Lastly, these CT antigens, especially MAGE-A4, may represent potential targets for cancer immunotherapy in patients with NSCLC.