The Pb isotope composition of the upper mantle beneath Central Europe is heterogeneous due to the subduction of regionally contrasting material during the Variscan and Alpine orogenies. Late Variscan to Cenozoic mantle-derived melts allow mapping this heterogeneity on a regional scale for the last ca. 340 Myr. Late Cretaceous and Cenozoic anorogenic magmatic rocks of the Bohemian Massif (lamprophyres, volcanic rocks of basanite/tephrite and trachyte/phonolite series) concentrate mostly in the Eger Rift. Cretaceous ultramafic lamprophyres yielded the most radiogenic Pb isotope signatures reflecting a maximum contribution from metasomatised lithospheric mantle, whereas Tertiary alkaline lamprophyres originated from mantle with less radiogenic 206Pb/204Pb ratios suggesting a more substantial modification of lithospheric source by interaction with asthenospheric-derived melts. Cenozoic volcanic rocks of the basanite/tephrite and trachyte/phonolite series define a linear mixing trend between these components, indicating dilution of the initial lithospheric mantle signature by upwelling asthenosphere during rifting. The Pb isotope composition of Late Cretaceous and Cenozoic magmatic rocks of the Bohemian Massif follows the same Pb growth curve as Variscan orogenic lamprophyres and lamproites that formed during the collision between Laurussia, Gondwana, and associated terranes. This implies that the crustal Pb signature in the post-Variscan mantle is repeatedly sampled by younger anorogenic melts. Most Cenozoic mantle-derived rocks of Central Europe show similar Pb isotope ranges as the Bohemian Massif.