The receptor for advanced glycation end products (RAGE) is a cell surface multiligand receptor of the immunoglobulin superfamily, which participates in physiological and pathological processes such as neuronal development, diabetes, inflammation, neurodegenerative disorders, and cancer. A novel splice variant of RAGE-endogenous secretory decoy form (esRAGE) was recently identified and is thought to be a prospective candidate to modify these RAGE-associated conditions. Here, we investigated the expression and distribution of esRAGE and RAGE proteins with domain-specific antibodies. We studied a wide variety of adult normal human preparations obtained from surgical and autopsy specimens using a tissue microarray technique. The results revealed that esRAGE was widely distributed and we classified its expression into four patterns. In pattern A, the cytoplasm is stained diffusely in neurons, vascular endothelium, pneumocytes, mesothelium, pancreatic beta cells, and macrophages/monocytes. In pattern B, dot-like granules are stained in the supranuclear regions facing the luminal surface of the bile ducts, salivary glands, digestive tracts, renal tubules, prostate, skin, thyroid, and bronchioles. Pattern C is represented by diffuse staining in the stromal area of the arterial walls. Pattern D shows diffuse and strong staining of secreted materials such as thyroidal colloid, crystals in renal tubular lumen, and glandular lumen in prostate. This study provides, for the first time, a histopathological basis for understanding the physiological roles of esRAGE in humans, and will contribute to elucidating the participation of esRAGE in pathological processes and to exploring novel diagnostic and therapeutic concepts.