Mutations in the APC gene give rise to familial adenomatous polyposis (FAP) and also occur in many, perhaps most, sporadic colon cancers. By screening with single-strand conformation polymorphism analysis we identified several mutations in a small region of the APC gene in both FAP and sporadic cancers. These mutations were either point mutations or small deletions or insertions causing frameshifts, and all generated stop codons. One 5 base-pair deletion was found in a sporadic colon tumour, a colorectal cancer cell line derived from a sporadic colon tumour, and in four unrelated FAP patients. This mutation produces distinctive heteroduplex bands, which can be detected with a simple non-radioactive assay. Our findings suggest that highly localised short sequences, essentially runs that code for adenine and thymine, may account for up to 20% of all observed APC mutations.