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A hospital-based case-control study on the possible relationship between cholecystectomy and colon cancer is described. In all, 569 cases and 1,129 controls were included in the study. Controls were patients who had been admitted either with another malignant disease (lung cancer or breast cancer), or because of benign gastrointestinal diseases. No differences with regard to colon cancer risk were observed between the two control groups. The crude odds ratio (OR) after cholecystectomy for colon cancer was 2.1 [95% CL (confidence limits) = 1.5; 2.9]. No significant difference in risk between males (OR = 2.0; 95% CL = 1.1; 3.6) and females (OR = 2.1; 95% CL = 1.4; 3.2) was found. A significant inverse relationship was found between the relative risk for colon cancer and sublocalization of the colon cancer, the highest relative risk (RR) found proximal in the colon. A decreasing risk with increasing interval between cholecystectomy and date of diagnosis of colon cancer was found. It is hypothesized that the apparent association between cholecystectomy and colon cancer does not reflect a necessary cause-effect relationship, but is rather an epiphenomenon representing a diminished exposure level to other etiologic factors.