The Kukaazi Pb–Zn–Cu–W polymetallic deposit, located in the Western Kunlun orogenic belt, is a newly discovered skarn-type deposit. Ore bodies mainly occur in the forms of lenses and veins along beddings of the Mesoproterozoic metamorphic rocks. Three ore blocks, KI, KII, and KIII, have been outlined in different parts of the Kukaazi deposit in terms of mineral assemblages. The KI ore block is mainly composed of chalcopyrite, scheelite, pyrrhotite, sphalerite, galena and minor pyrite, arsenopyrite, and molybdenite, whereas the other two ore blocks are made up of galena, sphalerite, magnetite and minor arsenopyrite and pyrite. In this study, we obtained a molybdenite isochron Re–Os age of 450.5 ± 6.4 Ma (2σ, MSWD = 0.057) and a scheelite Sm–Nd isochron age of 426 ± 59 Ma (2σ, MSWD = 0.49) for the KI ore block. They are broadly comparable to the ages of granitoid in the region. Scheelite grains from the KI ore block contain high abundances of rare earth elements (REE, 42.0–95.7 ppm) and are enriched in light REE compared to heavy REE, with negative Eu anomalies (δEu = 0.13–0.55). They display similar REE patterns and Sm/Nd ratios to those of the coeval granitoids in the region. Moreover, they also have similar Sr and Nd isotopes [87Sr/86Sr = 0.7107–0.7118; εNd(t) = −4.1 to −4.0] to those of such granitoids, implying that the tungsten-bearing fluids in the Kukaazi deposit probably originate from the granitic magmas. Our results first defined that the Early Paleozoic granitoids could lead to economic Mo–W–(Cu) mineralization at some favorable districts in the Western Kunlun orogenic belt and could be prospecting exploration targets. © 2017, Science Press, Institute of Geochemistry, CAS and Springer-Verlag GmbH Germany.