An immunohistological study showed differences in the expression of mucus-associated gastric M1 and intestinal M3 antigens between the proximal (100 cases) and distal (200 cases) colonic adenocarcinomas. Such a regional difference was not observed in the normal colon. A total of 55% and 78% of proximal tumours produced M1 and M3 antigens, respectively (versus 13% and 47% in the distal tumours). The high percentage of M1 positive proximal cancers could be explained by the higher percentage (i) of mucus-producing tumours, such as signet ring cell (6% vs 1%) or mucinous adenocarcinomas (29% vs 11%); and (ii) of M1(+) well-differentiated adenocarcinomas (45% vs 8.5%) and the presence of undifferentiated carcinoma producing M1 antigens (12% vs 0%). These latter carcinomas were found in older patients (mean age 78 years vs 66 years). These results suggest that, on the proximal side, the stem cells were more often engaged in a differentiation process involving the expression of M antigens than were those of the distal side. Moreover, the proximal stem cells more frequently produce a foetal differentiation program showing simultaneous expression of M3 and M1 antigens (in 48% of proximal tumours, vs 11.5% for the distal side). Around 12% of proximal adenocarcinomas (vs 2% of distal tumours) contained stem cells engaged in a cell differentiation program not observed in the normal adult or foetal colon, involving the predominant expression of M1 antigens associated with an undifferential histological pattern.