We have identified an antigen recognized by cytolytic T lymphocytes (CTL) on the autologous tumor cells of a nonsmall cell lung cancer patient. The antigenic peptide, presented by HLA‐B*5201 molecules, was encoded by a mutated sequence in the gene coding for the C subunit of transcription factor NF‐Y. The mutation was present in the tumor sample from which the cell line was derived, and appeared to be unique to the tumor of this patient. In a lymph node draining the tumor, precursors of CTL recognizing the autologous tumor cells were detected at a frequency of about 1/30,000 of the CD8 cells, and 85% of them recognized the mutated NF‐YC peptide, suggesting that the patient mounted a T cell response against this antigen. These results strengthened the notion that unique tumor‐specific antigens are highly represented not only in melanoma but also in other types of tumors, like nonsmall cell lung cancer. © 2005 Wiley‐Liss, Inc.