Abstract Mapping of the oxygen and carbon isotopic composition of hydrothermally altered wall rocks was conducted during blind ore prospecting for PbZn skarn deposits in the Kamioka mining district, central Japan. The wall rocks consist of heterogeneous rock units. Oxygen and carbon isotope ratios were determined for 35 limestones and 33 silicate rocks from the area around the Mozumi deposit (3 km × 3 km) in the Kamioka mining district. The results ( δ 18O spsmow of − 1.1 to + 17.3% and δ 13C sppdb of − 5.0 to +4.8% for limestones, and δ 18O spsmow of −0.8 to + 12.5% for silicate rocks) show isotope zonations of the wall rocks, with lighter isotopic compositions toward the center of mineralization. The isotope zonations likely formed by interaction of thermal waters with the wall rocks during skarn mineralization. The isotopically light zone indicates a higher paleotemperature or higher water-to-rock ratios, and occurs in the footwall of the 7Gohi fault. This structure is spatially related to the distribution of orebodies, indicating that the fault was the main conduit of the ore-forming fluids. The oxygen and carbon isotopic compositions of limestones vary regularly across limestone bodies hosted by the silicate wall rocks, suggesting that the thermal waters were pervasive throughout the wall rocks at the time of mineralization. An isotopically light zone was also found in the southeastern corner of the study area, where significant mineralization had yet to be identified. This suggested an extension of the extinct hydrothermal system to this area, and the possibility of hidden orebodies underneath. Recent drilling in this area has intercepted a zone 45 m thick with a grade of 13.4% Zn, 0.03% Pb and 8 g per metric ton at about 380 m depth.