K‐ras mutation‐positive (K‐ras+) and ‐negative (K‐ras−) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth‐related K‐ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of K‐ras+ and K‐ras− adenomas differs. K‐ras mutations in codons 12 and 13 were assessed in colorectal adenoma tissue (K‐ras+: n = 81, K‐ras−: n = 453). Dietary and lifestyle data were collected through questionnaires that were also administered to 709 polyp‐free controls. Multiple logistic regression analyses showed that intake of vitamin B2 and monounsaturated fat were differently associated with risk of K‐ras+ and K‐ras− adenomas; vitamin B2 was inversely associated with K‐ras− (highest vs. lowest tertile: odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.50–0.97, p trend = 0.020), but not with K‐ras+ adenomas, and a positive association with monounsaturated fat was confined to K‐ras− adenomas (OR = 1.57, 95% CI = 1.06–2.34, p trend = 0.029). Besides, potential, not statistically significant, differences in risk arose because red meat was distinctly positively associated with K‐ras+ adenomas (OR = 1.70, 95% CI = 0.94–3.09, p trend = 0.061); total dietary and polyunsaturated fat tended to be inversely associated with risk of K‐ras+ but not of K‐ras− adenomas; inverse associations with dairy products, calcium, protein and tea were confined to K‐ras− adenomas, and smoking was more markedly positively associated with K‐ras− adenomas. No differences in risk of K‐ras+ and K‐ras− adenomas could be detected for other factors. In conclusion, dietary and lifestyle factors may influence risk of K‐ras+ and K‐ras− adenomas differently. However, epidemiological literature on diet, lifestyle and colorectal K‐ras mutations is inconsistent. © 2006 Wiley‐Liss, Inc.