Intestinal epithelium contains several specialized cell types including M cells, which can be found in the follicle-associated epithelium (FAE) or occasionally on the villi. M cells are critical for sampling of intestinal flora and for transferring pathogens across the epithelial barrier for recognition by the immune system. Development of M cells on the villi (M-v) is independent of the presence of lymphocytes, while development of the FAE and M cells within the FAE (M-f) is dependent on B lymphocytes. Here, the concept is discussed that B cells are not required for induction of M-f differentiation but are required for transition to and maintenance of the mature M-f phenotype. Signaling pathways possibly involved in the B-cell-independent stages of M-cell development are also discussed.