MAL2, an integral membrane protein of the MAL family, is an essential component of the machinery necessary for the indirect transcytotic route of apical transport in human hepatoma HepG2 cells. To characterize the range of human epithelia that use MAL2-mediated pathways of transport, we carried out an immunohistochemical survey of normal tissues using a monoclonal antibody specific to the MAL2 protein. MAL2 expression was detected in specific types of normal epithelial cells throughout the respiratory system, the gastrointestinal and genitourinary tracts, in exocrine and endocrine glands, and in hepatocytes. Many different types of specialized secretory cells, either organized in discrete clusters (e.g., endocrine cells in the pancreas) or in endocrine glands (e.g., prostate), were also positive for MAL2. In addition to epithelial cells, peripheral neurons, mast cells, and dendritic cells were found to express MAL2. For comparison with normal epithelial tissue, different types of renal carcinoma were also analyzed, revealing alterations in MAL2 expression/distribution dependent on the particular histological type of the tumor. Our results allow the prediction of the existence of MAL2-based trafficking pathways in specific cell types and suggest applications of the anti-MAL2 antibody for the characterization of neoplastic tissue.