Large non-polypoid colorectal adenomas that spread over the mucosa and morphologically flat lesions are included in a group called granule-aggregating tumours. These are uncommon in the West. We aimed to clarify the biological differences between granule-aggregating tumours and colorectal polypoid adenomas. We evaluated the extent of apoptotic cell loss and expression of bcl-2 and p53 oncoproteins in 26 granule-aggregating tumours and 19 polypoid adenomas. The mean apoptosis index value of granule-aggregating tumours was significantly higher than that of polypoid adenomas. Only two (7.7%) granule-aggregating tumours and 13 (68.4%) polypoid colorectal adenomas expressed bcl-2, while 12 (46.2%) granule-aggregating tumours and six (31.6%) polypoid colorectal adenomas were p53-positive. Our results show that the higher apoptosis index and frequent expression of bcl-2 oncoprotein differentiates granule-aggregating tumours from polypoid colorectal adenomas. We propose that large non-polypoid granule-aggregating tumours of the colorectum are a biologically distinct entity.