BACKGROUND: The epidemiologic evidence for an etiologic role of fried foods and heterocyclic amines in colorectal carcinogenesis is inconsistent. PATIENTS AND METHODS: We have investigated the relation between fried foods and colorectal cancer risk using data from a large, multicentric case-control study conducted in Italy and Switzerland between 1992 and 2000, with 1394 cases of colon cancer, 886 cases of rectal cancer and 4765 controls. RESULTS: After allowing for major relevant covariates, the multivariate odds ratios (ORs) for an increment of one portion per week of fried foods were 0.97 [95% confidence interval (CI) = 0.93-1.01] for colon cancer and 1.04 (95% CI = 1.00-1.09) for rectal cancer. When we analyzed the type of fats mainly used for frying, we found that olive oil, but not other types of oils, appeared to protect from colon cancer risk (OR = 0.89, 95% CI = 0.82-0.98). CONCLUSIONS: Our results do not indicate a relevant role of fried foods on colorectal cancer risk. We found a possible favorable effect of (fried) olive oil on colon cancer risk but not on rectal cancer risk. [Authors]