Low-sulfidation epithermal mineralization on Milos (Aegean arc) records high paleofluid salinities that cannot be explained by a Broadlands-type low-salinity geothermal system. The δD and δ18O data do not document 18O-shifted meteoric waters, one of the characteristic features in terrestrial geothermal systems. Nor is a submarine origin indicated—stable isotope data show mixing of meteoric, seawater, and volcanic-arc gases. Strontium isotope data are comparable to those of a nearby active seawater-entrained geothermal system. These are features seen in hydrothermal systems associated with emergent volcanoes. The similarities between ancient and active systems on Milos in terms of salinity, δD vs. δ18O, and strontium isotope systematics strongly suggest that seawater is the main source for Na and Cl. We suggest that geothermal systems containing seawater associated with emergent volcanoes are an additional analog for intrusion-centered ore-deposit models. Furthermore, such systems bridge the gap between submarine and terrestrial geothermal systems—the modern analogs for volcanic-hosted massive sulfide and epithermal mineralization in the scheme of intrusion-centered hydrothermal mineralization.