The human genes MAGE-1 and -3 encode melanoma peptide antigens that are recognized by autologous cytotoxic T lymphocytes. Tumors expressing MAGE genes are potential targets for cancer immunotherapy, because MAGE genes are expressed only in tumor tissue and not in any normal tissue except testis and placenta. However, little is known about MAGE gene expression in human esophageal carcinoma. The purpose of this study was therefore to analyze MAGE gene status in human esophageal carcinoma. We studied the expression status of these genes in 42 surgical samples and in 12 cell lines of human esophageal carcinoma using the reverse transcription polymerase chain reaction (RT-PCR). Various clinicopathological factors were also analyzed. No MAGE gene expression was seen in any of the 42 normal esophageal tissue specimens. In contrast, tumor tissue expressed MAGE-1, -2, and -3 in 26, 18 and 24 specimens, respectively. Thirty-three of 42 tumors expressed at least one MAGE gene. Significant clinicopathologic differences between the tumors were not observed, regardless of the presence or absence of MAGE gene expression. In cell lines, MAGE-1, -2, and -3 gene expression was recognized in 5, 4 and 4 cell lines, respectively. This study demonstrates that MAGE genes are frequently expressed in clinical samples as well as in cell lines of esophageal carcinoma. The identification of MAGE genes, therefore, may open up a new modality of treatment, namely specific immunotherapy, for patients with esophageal carcinoma.