During infection of the intestine, MUC1 is expressed de novo, which aids in the protection against pathogens. This mucin is also, however, aberrantly expressed in many cancers. Thus its functions have many facets, both protecting against disease while being associated with others. This study examined the effects of overexpressing full length MUC1 in two colon cancer cell lines with very low/no endogenous MUC1 expression: HT29, LS174T, and a third, LS513, which does express low endogenous levels. Unexpectedly, MUC1 caused a slower proliferation rate in the HT29 cells, however there was little effect on the growth rate of the LS174T or LS513 cell lines. There was a drastic change in morphology in the HT29 cells, taking on a fibroblast appearance, which suggested epithelial to mesenchymal transition (EMT) was occurring, a process that has been shown to be induced by MUC1 in other types of cancer cells. Examining the expression of epithelial and mesenchymal markers confirmed that EMT was indeed induced in these cells. MUC1 led to an increased resistance to DNA damage-induced apoptosis in the HT29 cells, consistent with the phenotypic response of cells that have undergone EMT. While the LS174T cells did not have as distinctive a change in morphology, there was an increase in expression of mesenchymal markers, indicating EMT was also occurring in these cells. The LS513 cells, however, did not have any change in morphology, growth rate or resistance to apoptosis, showing that the effect of MUC1 differs between cells. This suggests that it is aberrant expression, rather than overexpression, of MUC1 that has the greatest effect on colon cancer cells.