Recent studies have suggested that the presence of a c-Kit/c-Kit ligand autocrine loop may be an important regulator of proliferation and progression of human colorectal cancer, capable of affecting the prognosis of these patients. If present, the c-Kit alteration may provide a suitable target for therapy, similar to what has been observed in gastrointestinal stromal tumors. To determine the incidence of c-Kit expression in human colorectal carcinomas, we studied the immunohistochemical c-Kit expression in a selection of 126 colorectal carcinomas of different stage, using stage-oriented human cancer tissue microarrays. Formalin-fixed, paraffin-embedded tissues of each case were immunostained using the avidin-biotin-peroxidase method and the antihuman c-Kit (CD117) rabbit polyclonal antibody. High cytoplasmic c-Kit staining (Allred score of 7-8) was observed in 1.6% of the colon carcinoma patients evaluated. The c-Kit-positive tumors were poorly differentiated carcinomas arising at the anorectal junction. The remaining tumors revealed no detectable expression of c-Kit. Twenty-seven non-neoplastic tissues, normal colonic mucosa, and adenomas were also CD117 negative. We show the rare expression of c-Kit in normal and neoplastic colorectal tissues, suggesting that routine screening for c-Kit by immunohistochemistry to identify c-Kit-positive carcinomas may be cost ineffective. However, further study of c-Kit expression in poorly differentiated colon cancers may be useful since these generally chemoresistant tumors may respond to therapy with inhibitor compounds directed against c-Kit.