Peyer’s patch follicle‐associated epithelium (FAE) regulates intestinal antigen access to the immune system in part through the action of microfold (M) cells which mediate transcytosis of antigens and microorganisms. Studies on M cells have been limited by the difficulties in isolating purified cells, so we applied TOGA mRNA expression profiling to identify genes associated with the in vitro induction of M cell‐like features in Caco‐2 cells and tested them against normal Peyer’s patch tissue for their expression in FAE. Among the genes identified by this method, laminin β3, a matrix metalloproteinase and a tetraspan family member, showed enriched expression in FAE of mouse Peyer’s patches. Moreover, the C. perfringens enterotoxin receptor (CPE‐R) appeared to be expressed more strongly by UEA‐1⁺ M cells relative to neighboring FAE. Expression of the tetraspan TM4SF3 gene and CPE‐R was also confirmed in human Peyer’s patch FAE. Our results suggest that while the Caco‐2 differentiation model is associated with some functional features of M cells, the genes induced may instead reflect the acquisition of a more general FAE phenotype, sharing only select features with the M cell subset.