PURPOSE:The majority of colorectal neoplasms diagnosed are adenocarcinomas. Other histologies such as squamous, adenosquamous, carcinoid tumors, or lymphoid tumors are occasionally identified. Given the rarity of squamous‐cell tumors, it is very difficult to study their natural course and response to therapy. An attempt is made to describe the frequency, anatomic location, and response to therapy with a review of the literature.METHODS:From the Cancer Registry at the University of Missouri‐Columbia Ellis Fischel Cancer Center, tumors of the colon identified above the dentate line were selected for chart review. Data were extracted from cases between the years 1940 and 1996. The key terms used to identify cases were epidermoid, squamous cell, and cancer of the rectum or colon. Using this approach, forty patients were identified and each record was reviewed.RESULTS:The majority of these cases were anal cancers with proximal extension into the rectum and were excluded. Of 4,561 cases of epithelial colon and rectal cancers identified, only one additional case of squamouscell cancer could be verified. In this report we describe a patient with a primary squamous‐cell carcinoma of the sigmoid colon with metastatic disease to the liver at diagnosis who responded to systemic chemotherapy. We believe this to be the first reported case of this rare tumor type in which the patient's tumor responded to systemic chemotherapy. Two cases with a thorough review of literature are presented.CONCLUSIONS:Primary squamous‐cell carcinoma of the colon is a rare malignancy of unknown cause and pathogenesis. Metastatic tumors to the colon should be ruled out in all cases before therapy. Early detection and surgery remain the main therapeutic options, but as presented in our case, response to chemotherapy in advanced disease is encouraging.