The spontaneous immune responses against XAGE‐1b (GAGED2a) were analyzed in non‐small cell lung cancer (NSCLC) patients. An antibody response against XAGE‐1b (GAGED2a) was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma patients. A CD4 T‐cell response was detected in 88% (14/16) and a CD8 T‐cell response in 67% (6/9) in the XAGE‐1b (GAGED2a) antibody‐positive patients examined. Frequent antibody responses and CD4 and CD8 T‐cell responses in XAGE‐1b (GAGED2a) antibody‐positive patients indicate the strong immunogenicity of the XAGE‐1b (GAGED2a) antigen in NSCLC patients. We established T‐cell clones from PBMCs of antibody‐positive patients and determined the DRB1*04:05‐restricted XAGE‐1b (GAGED2a) 18–31 peptide (14‐mer) as a CD4 T cell epitope and the A*02:06‐restricted XAGE‐1b (GAGED2a) 21‐29 peptide (9‐mer) as a CD8 T cell epitope. As for peptide recognition, CD4 and CD8 T‐cell clones responded to naturally processed antigen. The CD4 T‐cell clone recognized DCs pulsed with the synthetic protein or a lysate from XAGE‐1b‐transfected 293T cells. The CD8 T‐cell clone showed cytotoxicity against a tumor expressing XAGE‐1b (GAGED2a) and the appropriate HLA class I allele. These findings establish XAGE‐1b (GAGED2a) as a promising target for a lung cancer vaccine.