Activating mutations in the Ki-ras2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki-ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki-ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki-ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.