The M cell is a remarkable cell type found in the epithelium that covers mucosa-associated lymphoid tissue in the digestive tract and the airways. M cells internalize macromolecules and microorganisms efficiently and deliver them to the underlying lymphoid tissue. In the gut, M cells, unlike the neighbouring absorptive enterocytes, lack a highly organized apical brush border and glycocalyx, and are poorly equipped with digestive enzymes. An insight into the role of immune cells in the differentiation of this unique cell type has been gained recently by using immunodeficient mice and an in vitro model of M cells. These and other recent findings suggest that M cells have a highly plastic phenotype and raise interesting questions about how cell differentiation is controlled in the gut.