Overexpression of KIT protein (CD117), the product of the c-kit gene, has been shown to have important prognostic and therapeutic implications for a number of malignant neoplasms. Previous studies have shown conflicting results regarding the expression of c-kit in malignant mesothelioma. To determine whether malignant mesothelioma expresses KIT, immunohistochemistry and RT-PCR were used to analyze archived tissue from 37 cases of mesothelioma. Although a subset of mesotheliomas demonstrated specific staining with the DAKO anti-KIT antibody, in each case staining was nuclear. We could not detect c-kit mRNA by a sensitive RT-PCR assay, even in cases with strong nuclear staining. Furthermore, a second anti-KIT antibody (Cell-Marque) only demonstrated staining in a single mesothelioma case and in none of the cases that demonstrated nuclear staining. We conclude that immunoreactivity for KIT in mesothelioma does not represent expression of the c-kit gene and may represent antibody cross-reaction with nuclear proteins. Our results raise doubt about previously reported expression of KIT in mesothelioma and consequently, the applicability of therapeutic agents that target the kinase activity of KIT.