Neoplastic, inflammatory and regenerative processes affecting colorectal mucosa are associated with alterations in structure of epithelial mucin. This review collates mucin-, lectin-, and immuno-histochemical observations on colorectal mucins and introduces recent molecular genetic insights into the structure of the protein backbone of mucins. The numerous structural modifications uncovered by the various technical approaches have been reduced to a few manageable principles that are of relevance to both researcher and diagnostic pathologist. Particular attention is drawn to the need to appreciate the limited specificities of probes, the confounding influences of anatomical site and genetic factors (necessitating the use of appropriate positive and negative control tissues) and the precise location of secretory material. In the past, insufficient attention has been given to the effects of altered differentiation including metaplasia and differing lineage expression in epithelial disorders of growth. It is likely that certain changes loosely ascribed to goblet cell mucin, such as neo-expression of blood group antigens and anomalous expression of core carbohydrate structures, do not occur at all. Critical examination of available data point to only two consistent and unequivocal changes affecting goblet cell mucin in pathological processes: loss of O-acetyl substituents at sialic acid C4 and C7,8,9 and increased sialylation. Furthermore, there are no neoplasia-specific alterations in mucins documented to date. All neoplasia-associated changes have been described in non-neoplastic lesions also.