To date, the earliest mutations in colorectal adenomas have been found in the adenomatous polyposis coli (APC) gene, considered the 'gatekeeper' in tumourigenesis. To study the types of APC gene mutations and their relation to clinicopathological features which are associated with malignant potential, the mutation cluster region of the APC gene was analysed in a series of 32 human sporadic colorectal adenomas from 22 patients. DNA was extracted from frozen sections and two overlapping fragments which cover the mutation cluster region were amplified using the polymerase chain reaction (PCR). Mutations were screened with temperature gradient gel electrophoresis and identified by DNA sequencing. Mutations were found in 14 samples (44 per cent) from 11 patients. The changes could be characterized as point mutations (n = 7), deletions of one or more nucleotides (n = 6), and insertions (n = 1). From five patients, multiple adenoma samples were obtained and the adenomas from two of these patients showed a heterogeneous mutation pattern in the APC gene. All detected mutations are predicted to result in a truncated APC protein. Genetic alterations in the mutation cluster region of the APC gene occurred significantly more frequently in large adenomas and showed a trend towards an increase in villous adenomas and adenomas with moderate and severe dysplasia. It is concluded that an increased proportion of APC gene mutations were found in the adenomas showing clinicopathological features associated with increased proliferation but not with characteristics of malignant potential. The results suggest that in a significant proportion of adenomas, other (genetic) alterations are involved in early tumourigenesis.