Display omitted •91500 is an ideal reference material for garnet U-Pb dating in spot sizes of 32–16 μm.•Willsboro is not suitable to calibrate the garnets with relatively high common lead.•Anji skarn system (137–138 Ma) has a genetic relationship with fine-grained granite.•Mantle-sourced materials may play an important role to form the Anji skarn system. Garnet becomes an important tool to analyze the timing and genesis of metamorphic rocks (especially skarn deposits), clastic sediments, and igneous rocks due to its common occurrence. However, for in-situ U-Pb dating of garnet, is there any difference to use 91500 or Willsboro as a primary standard and can a robust age be obtained for low-U (≤ 10 ppm) garnet as Willsboro and Mali in small spot sizes of 32–16 μm? Can garnet U-Pb dating be used to exactly identify the ore-related intrusive unit in an intrusive complex and its related distal skarn system setting? In this contribution, Willsboro, Mali, QC04, and three other andradite samples WMQ-2(3), WSG-1, and YJ-4(2) from the Anji polymetallic skarn deposit were analyzed to discuss these questions. In our analysis, zircon 91500 is confirmed as reliable reference material for these garnets in spot sizes of 32–16 μm. Notably, both 91500 and Willsboro are suitable as primary standards for the garnets as Mali and QC04, which have extremely low common lead and are mainly plotted at the lower intersection in the Tera-Wasserburg Concordia diagram; Willsboro is not suitable to calibrate the garnets as WMQ-2(3), WSG-1, and YJ-4(2), which contain relatively high common lead and fall along a mixing line between initial common Pb and radiogenic components in the Tera-Wasserburg Concordia diagram. In the Anji polymetallic system, based on garnet U-Pb, mica Ar-Ar and previous zircon U-Pb dating, proximal Pb-Zn-Ag-Cu and distal Fe and Fe-Zn-Cu skarn deposits were formed by the same magmatic-hydrothermal-mineralization event at 137–138 Ma. These ages, geological evidences, our and previous lead isotopic compositions confirm that Fe, Fe-Zn-Cu, Pb-Zn-Ag-Cu, Mo, and fluorite-chalcedony mineralization have genetic relationships with fine-grained granite. Compared with other units of the Wushanguan complex, the lead isotopic compositions indicate that fine-grained granite supplies most ore-forming materials, and the increased mantle-sourced materials may play an important role in the formation of the Anji skarn system.