© 2018 Society of Economic Geologists, Inc. Vein and stratabound Zn-Pb sulfides are hosted within siliciclastic rocks and marine carbonates of Cretaceous age and within caprock carbonates at the margins of the Murguía and Orduña saline diapirs in the Basque-Cantabrian basin. Organic matter is ubiquitous, and textures indicate a genetic link to sulfide precipitation. Sulfides (pyrite, sphalerite, and galena) precipitated from brines with halogen ratios compatible with halite dissolution. Thermal indicators (fluid inclusion, organic matter, and sulfur isotope data), point to formation temperatures between 150° and 200°C. The d34S values of sphalerite and galena (4.1–15.1) suggest a sulfur source related to the reduction of evaporite sulfate (thermochemical sulfate reduction) of Triassic age (15.3–17.4). The interaction of carbon-poor, metal- and sulfate-bearing hot brines with host rocks activated the cracking of organic matter, triggering sulfide precipitation at a rate controlled by the H2S production. Textural relationships suggest that ore precipitation was related to dolomitization of host rocks (siliciclastic rocks, marine carbonates, and caprock). The d13C and d18O of carbonates range from 3.5 to –20.5 and from 16.1 to 28.7, respectively, indicative of different carbon sources and host-rock types. Carbonates associated with sulfide mineralization depict d13C/d18O assemblages and 87Sr/86Sr ratios (0.70801–0.71202) resulting from the interaction of a basinal brine with the different host rocks. Galena Pb isotope ratios—206Pb/204Pb from 18.643 to 18.696, 207Pb/204Pb from 15.650 to 15.676, and 208Pb/204Pb from 38.720 to 38.780—point to metal source rocks similar to other Mississippi Valley-type (MVT) deposits of the Basque-Cantabrian basin. Sulfide concentrations around the Murguía and Orduña diapirs are not concomitant with caprock formation but with dolomitization, as in MVT deposits. This is in contrast with the diapir-related deposits of the Gulf Coast and shares characteristics with the diapir-related mineralization in North Africa.