The Cuonadong deposit is located in southern Tibet and represents the first large-scale tin polymetallic deposit in the Himalayan region. Sn-(W) skarn mineralization is spatially related to leucogranites, whereas Be-Nb-Ta mineralization mainly develops in pegmatites. Alteration and veining in this deposit can be divided in to five stages: prograde skarn (stage I), retrograde skarn (stage II), cassiterite-quartz vein (stage III), cassiterite-sulfide vein (stage IV) and fluorite quartz vein (stage V). 40Ar39Ar dating of muscovite from the skarn and phlogopite from the cassiterite-sulfide vein yield isochron ages of 15.4 ± 0.3 Ma and 15.0 ± 0.3 Ma, respectively, whereas UPb dating of cassiterite from the skarn yields a Tera-Wasserburg low-intercept precise age of 14.2 ± 0.2 Ma. Zircon and monazite UPb ages of the causative stanniferous leucogranites are 15.3 ± 0.1 Ma and 14.9 ± 0.2 Ma, respectively. Mineralization ages are consistent with the emplaced ages of the granites within the analytical uncertainties, which indicates that the tin polymetallic mineralization is genetically related to the Miocene leucogranites. Sn-bearing leucogranites have zircon εHf(t) values that vary from −13.3 to −8.5 (-10.7 on average), with an average TDM2 value of 1.56 Ga, which reveals that the leucogranites are derived from partial melting of ancient metasedimentary rocks. According to the zircon trace elements, the Miocene leucogranites are highly differentiated reduced S-type granites that formed at relatively high temperature. The average homogenization temperatures of fluid inclusions in different minerals that formed at stages II, III, IV and V are 351, 315, 240 and  175 °C, respectively, whereas their salinities are 8.3, 4.9, 9.5 and 3.8 wt% NaCl equiv., respectively. The C-H-O-S-Pb isotopes indicate that the ore-forming fluid and materials mainly originated from Miocene leucogranite. Dehydration and partial melting of mica in the Greater Himalayan crystalline complex due to east-west extension at 18–14 Ma developed the stanniferous leucogranite and ore-controlling fault system. Because of the pervasive occurrence of gneiss domes and Miocene Sn-bearing leucogranites similar to Cuonadong, the Himalaya has strong potential to be a new globally important Sn-(W) rare metal metallogenic belt. Display omitted •Tin polymetallic mineralization dated as ca. 15 Ma.•Mineralization genetically related to fractionated Miocene leucogranites.•Ore-forming materials of crustal origin.•Himalayan leucogranites belt has great potential for Sn polymetallic ore deposits.