Peraluminous orthogneisses represent a typical rock type of the Monotonous and Varied units of the Moldanubian Zone. The most probable setting for the generation of these rocks is the Cambro-Ordovician magmatic event linked to crustal anataxis, which is related to the thermal relaxation of thickened continental crust. According to their geological position, the mineralogy and geochemistry can be traced to the Blanik and Destna type orthogneisses. The Blanik type is represented by muscovite-biotite to muscovite-tourmaline orthogneisses whose granitic protolith can be generated by muscovite-dominant dehydration melting of metapelites. The chemical heterogeneity of this type suggests magma differentiation, which is manifested by the presence of P-Li-Sn-Nb mineralization. Muscovite-biotite to biotite Destna type orthogneisses were likely generated by the fluid-present melting of immature crustal sources (e.g. metagreywackes and metaigneous rocks) and spatially related to small occurrences of W-bearing mineralization. We applied whole-rock geochemistry combined with mineralogy and zircon U-Pb geochronology to the evolutionary interpretation of one of the most fractionated bodies of Destna type orthogneisses situated near the village of Pacov. The Pacov orthogneiss is accompanied by pre-Variscan greisens and related tungsten mineralization (ferberite, scheelite, pyrite, and native bismuth). The mineral assemblages of these rock types are modified by the Variscan metamorphic overprint (720 ± 75 °C at 0.65 ± 0.29 GPa). Two petrographically distinct samples of orthogneisses give U–Pb zircon ages of 494 ± 2 Ma (garnet-muscovite orthogneiss) and 485 ± 4 Ma (muscovite-biotite orthogneiss). The abundance of inherited pre-magmatic zircon cores (∼614–578 Ma) most likely documents detrital protoliths derived from erosion of the Ediacaran volcanic arc.