In the Pioche district, lead, zinc, silver, gold, copper, and manganese were mined from intrusion-related bedding replacement, fissure replacement, and fissure vein deposits in Late Proterozoic and Cambrian siliciclastic and carbonate rocks. Radioisotopic ages of intrusions, lead and sulfur isotope compositions of sulfide minerals, and metal abundances define two periods of metal mineralization: Late Cretaceous (ca. 100 to 90 Ma) and late Oligocene (ca. 28 to 27 Ma). Cretaceous deposits are characterized by spatial association with Cretaceous dikes and small stocks, high sulfur isotope compositions of sulfide minerals (delta 34 S > 10ppm), mostly radiogenic lead isotope compositions ( 207 Pb/ 204 Pb > 15.65), stratigraphic distribution restricted to Late Proterozoic-Early Cambrian rocks, and in many cases, low abundances of copper. Unifying features of Oligocene deposits are proximity to Oligocene intrusions and buried, magnetic apophyses of Oligocene intrusions, low sulfur isotope compositions (delta 34 S <8ppm), tightly grouped, relatively nonradiogenic lead isotope compositions ( 207 Pb/ 204 Pb <15.65), stratigraphic distribution that includes Late Proterozoic through Late Cambrian siliciclastic and carbonate rocks, and significant copper production.Structural analyses of the Pioche district and of adjacent ranges, combined with oil well exploration holes, intrusion ages, lead and sulfur isotope compositions, and Pioche district magnetism, allow for tens of kilometers or more of eastward displacement of Late Proterozoic, Cambrian, and late Paleozoic siliciclastic and carbonate rocks prior to the late Oligocene. These rocks now underlie the Pioche district, along two low-angle detachment faults. Lead and sulfur isotope compositions of ores and disseminated pyrite in subjacent Late Proterozoic-Early Cambrian and late Paleozoic siliciclastic and carbonate rocks permit derivation of the ore lead and sulfur from these rocks in proportions that approximately correspond to ages of associated intrusions and to timing of structural stacking of subjacent rocks. Late Cretaceous metal deposits at Pioche have been apparently decoupled from associated granitic intrusions, but late Oligocene ores are intact relative to the Blind Mountain stock and other Oligocene intrusions. Lead and sulfur isotope compositions of deposits at Pioche and in other multiple-intrusion mining districts in the Great Basin may provide valuable exploration guidance, with careful attention to intrusion ages and to hydrothermal mineral parageneses.