The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet. The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible association between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms. With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand conformation polymorphism approach. A polychotomous logistic regression model was used to assess the significance of observed differences between wild-type and mutated tumors with respect to population controls in the different categories of nutrient consumption. Multivariate density models were used to adjust the correlation between nutrients and total energy. Our studies show that high consumption of monounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-type Ki-ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high calcium intake is associated with a decreased risk of Ki-ras mutated tumors but not of wild-type tumors. Tumor genotyping can reveal epidemiological associations that are weak or unapparent when cases-control studies are not stratified by tumor genotype.