The Václav vein (Březové Hory deposit, Příbram ore area, Czech Republic) is a base–metal vein containing minor Cu-Zn-Pb-Ag-Sb sulfidic mineralization in a usually hematitized gangue. A detailed mineralogical study using an electron microprobe revealed a complicated multistage evolution of the vein. Early siderite and Fe-rich dolomite were strongly replaced by assemblages of hematite+rhodochrosite and hematite+kutnohorite/Mn-rich dolomite, respectively. In addition, siderite also experienced strong silicification. These changes were associated with the dissolution of associated sulfides (sphalerite, galena). The following portion of the vein contains low-Mn dolomite and calcite gangue with Zn-rich chlorite, wittichenite, tetrahedrite-group minerals, chalcopyrite, bornite, and djurleite, again showing common replacement textures in case of sulfides. The latest stage was characterized by the input of Ag and Hg, giving rise to Ag-Cu sulfides, native silver (partly Hg-rich), balkanite, and (meta)cinnabar. We explain the formation of hematite-bearing oxidized assemblages at the expense of pre-existing “normal” Příbram mineralization due to repeated episodic infiltration of oxygenated surface waters during the vein evolution. Episodic mixing of ore fluids with surface waters was suggested from previous stable isotope and fluid inclusion studies in the Příbram ore area. Our mineralogical study thus strengthens this genetic scenario, illustrates the dynamics of fluid movement during the evolution of a distinct ore vein structure, and shows that the low content of ore minerals cannot be necessarily a primary feature of a vein.