Volcan Mocho-Choshuenco, a Pleistocene-Holocene basaltic andesite to dacite shield volcano located at lat 40°S in the Southern Volcanic Zone (SVZ) of the Andes, is built on the thinnest SVZ continental crust (≈30 km), which consists largely of Paleozoic sedimentary and metamorphic rocks and Mesozoic plutons. Sr, Pb, Nd, and O isotopic ratios of Mocho-Choshuenco lavas (87Sr/86Sr = 0.70399 to 0.70422; 206Pb/204Pb =18.57 to 18.61; 207Pb/204Pb = 15.60 to 15.63; 208Pb/ 204Pb = 38.45 to 38.57; 143Nd/ 144Nd = 0.512787 to 0.512881; δ18O = +5.8‰ to +6.8‰ Standard Mean Ocean Water) are similar to those of other SVZ centers and exhibit no correlation with indices of differentiation. However, incompatible trace-element systematics indicate that evolved lavas have been contaminated by crustal plutonic rocks by 5% to 15%. Rb/Ba, K/Ba, Rb/La, and K/La ratios increase with increasing SiO2 content as a result of assimilation of orogenic calc-alkalic plutonic rocks enriched in Rb and K relative to Ba and La. Xenoliths of plutonic rocks recovered from Mocho-Choshuenco lavas are slightly more radiogenic in 87Sr/86Sr, less radiogenic in 143Nd/144Nd, and comparable in Pb isotopic ratios, and they have variable 18O contents (87Sr/86Sr = 0.70482 to 0.70557; 206Pb/204Pb = 18.60 to 18.64; 207Pb/204Pb = 15.60 to 15.62; 208Pb/204Pb = 38.53 to 38.56; 143Nd/144Nd = 0.512686; δ18O = +3.3‰ to +5.5‰ SMOW). Contamination of Mocho-Choshuenco parental magmas by crustal melts with small isotopic contrast imposed little variation on isotopic heterogeneities existing in the parental compositions. These heterogeneities probably were produced during magma-crust interaction at the crust-mantle boundary or in the lower crust.