In regions where crystalline basement is not well exposed, radiogenic isotope data from high-level igneous rocks can provide important information about the underlying crust, even if only modest amounts of crustal assimilation have occurred. One such region is northwestern Mexico, where cover sequences and younger tectonic features obscure the southern margin of the North American craton. Within the heart of the Sierra Madre Occidental volcanic field in northwestern Mexico, ranges of isotope ratios from the 38–29 Ma Tomóchic volcanic center in west-central Chihuahua, are ϵ Nd, +2.3 to −5.2 (with only one value < −3.0); 87Sr/86Sr, 0.7043–0.7089 (with only one value > 0.7070); 206Pb/204Pb, 18.49–18.80; 207Pb/204Pb, 15.56–15.62; and 208Pb/204Pb, 38.35–38.79. These values are unlike those of xenolith-bearing, primitive, mantle-derived magmas from either the southwestern United States or northern Mexico, and are interpreted to reflect modest crustal interaction, even in the least evolved compositions (basaltic andesite). Volcanic rocks of the Tomóchic volcanic center have less radiogenic Sr and more radiogenic Nd than rocks from calc-alkaline, mid-Tertiary, ash-flow tuff provinces in the southwestern United States that were erupted through the 1.8–1.0 Ga North American Precambrian craton (Laurentia). The Pb isotopic compositions of the Tomóchic volcanic center have a restricted range and closely resemble those for volcanic rocks in eastern Chihuahua and west Texas that were erupted through the basement of the Coahuila block, which is outboard of the Ouachita front in the region. These results eliminate the possibility that Laurentia continues southward beneath the Tomóchic area. We suggest instead that the younger basement to the south of the Ouachita front continues into western Chihuahua, although a regional isotopic study is needed to demonstrate the continuity of this configuration.