The Erzgebirge region of Germany records two major episodes of hydrothermal activity, which includes a Late Carboniferous to Early Permian event associated with significant Sn-W mineralization that is related to late Variscan granite magmatism, and a Mesozoic episode of polymetallic vein mineralization. In contrast to the first event, the age of the younger hydrothermal activity is poorly constrained. For the latter, various geochronological methods yielded a wide age range from Permian to early Tertiary. Here we apply fluorite (U-Th-Sm)/He thermochronology (FHe) on both types of mineralization with a twofold goal: (1) to investigate the sensitivity and applicability of the new FHe method (Evans et al., 2005), and (2) to constrain the thermal history of ore deposits in the Erzgebirge region. Two hundred and thirty-three aliquots from seven mineralization localities have been dated. Fluorite from six deposits yielded Cretaceous FHe ages between 112 to 79 Ma, which are independent of their paragenesis. In contrast, fluorite from the Sadisdorf Sn-W deposit yielded an age of 234 Ma. The younger ages are interpreted as cooling ages indicating the time of the last thermal overprint, including possible hydrothermal activity, in the Erzgebirge. The oldest, Triassic FHe ages at Sadisdorf indicate that the Mesozoic thermal overprint only partially reset the (U-Th-Sm)/He system of the late Variscan mineralization. Thermal modeling based on FHe ages and He diffusion parameters in fluorite results in thermal histories comparable to the results from the well-established apatite-based thermal modeling. This study emphasizes the applicability of fluorite (U-Th-Sm)/He thermochronology, which is especially suited for ore deposits where apatite is lacking.