Lead isotope variability of magmatic arc rocks and associated mineralization of the Central Andes is usually considered to be the result of mixing between a homogeneous mantle and heterogeneous continental crust. About 230 new lead isotope data on the Northern and Central Andes allow us to compare for the first time lead isotope systematics of the Late Cretaceous – Tertiary arc magmatism and associated mineral- ization along the Andean chain between 8°N and 40°S. Lead isotope compositions indicate mixing between mantle and upper crustal rocks along the whole Andean chain. Additionally, we have found that mantle end-members of the Late Creta- ceous – Tertiary magmatism are heterogeneous and systemat- ically shifted towards less radiogenic 206Pb ⁄ 204Pb compositions from north to south along the Andes. This heterogeneity most likely results from mixing between a low radiogenic mantle, possibly carrying a DMM or EM I component, and a more radiogenic mantle, possibly carrying an HIMU component. Thus, our results imply that lead isotope variability of Andean magmas at the continental scale is caused not only by crustal but also by mantle heterogeneity.