The presence of S100 protein in the kidney of Philippine swamp buffalo (Bubalusbubaliscarabanensis) was detected using immunohistochemistry. The Avidin-Biotin Peroxidase complex method was carried out with a polyclonal antibody against S100 protein. S100 immunoreactivity was present in the thin loop of Henle, collecting ducts and tubules. Positive immunoreaction was also detected in erythrocytes and endothelial lining cells of arcuate artery and vein, interlobular artery and vein, venules, glomerular and peritubular capillaries. This is the first report of the detection and distribution of S100 protein in the swamp buffalo kidney. This study confirms that S100 can be found extraneurally and can be a useful marker for anatomic pathology.