A change in sialic acid, notably loss of O acetyl substitution, was studied histochemically in a series of 93 colorectal adenomas that included 14 malignant polyps. Changes in sialic acid were uncommon in adenomas showing mild dysplasia but became increasingly common in moderately and severely dysplastic adenomas and were always present in carcinomatous areas. There was no correlation between a change in sialic acid and either size or villous architecture of benign adenomas. As mucin change often preceded the development of invasive cancer, it could not be used on its own to distinguish between epithelial displacement (pseudoinvasion) and malignant invasion. An abundant luminal accumulation of altered sialic acid in association with an epithelial lining that was non-mucin secreting, however, was specific for cancer. Conversely, the presence of unchanged intracellular or intraluminal O-acetyl sialic acid may help to exclude a diagnosis of malignancy in equivocal cases. The change is not specific for colorectal neoplasms and probably represents a metaplasia to a small intestinal phenotype.