We report on the application of the U-Th-He method for the direct dating of pyrite and provide an original methodological approach for measurement of U, Th and He in single grains without loss of parent nuclides during thermal extraction of He. The U-Th-He age of ten samples of high-crystalline stoichiometric pyrite from unoxidized massive ores of the Uzelga volcanogenic massive sulfide (VMS) deposit, South Urals, is 382 ± 12 Ma (2σ) (U concentrations ~1–5 ppm;4 He ~10−4 cm3 STP g−1). This age is consistent with independent (biostratigraphic) estimations of the age of ore formation (ca, 389–380 Ma) and is remarkably older than the probable age of the regional prehnite-pumpellyite facies metamorphism (~340–345 Ma). Our results indicate that the U-Th-He dating of ~1 mg weight pyrite sample is possible and open new perspectives for the dating of ore deposits. The relative simplicity of U-Th-He dating in comparison with other geochronological methods makes this approach interesting for further application. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.