Cap43 protein has been proven to be upregulated by nickel compounds or hypoxic stress, often during cell differentiation or cell growth arrest. However, the function of this gene remains unknown. Although, several studies have been performed, none of these have evaluated the expression of Cap43 in esophageal cancer. To clarify its function and role in esophageal cancer, a clinical archive of cancer specimens was examined for the expression of Cap43 by immunohistochemistry. The expression level of Cap43 protein was also investigated by Western blotting and mRNA by realtime RT-PCR using esophageal cancer cell lines. Immunohistochemistry results showed that overexpression of Cap43 was correlated with malignant status of esophageal cancer and that was considered as an independent prognostic marker. Interestingly, adenocarcinoma of the esophagus did not express Cap43. In esophageal cancer cell lines, Western blotting and real-time RT-PCR, showed a variation in the expression level of Cap43 and there was no obvious correlation between protein and mRNA levels. The present report shows for the first time that the expression of the Cap43 gene has a function in tumor progression and that its expression correlates independently with patient survival. Cap43 gene could be considered as a new and important cancer marker.