Deposit of CaSO 4 in hydrometallurgical processes involving heavy metals usually decreases production quality and harms the production process. To avoid its formation at false time and sites, a sound understanding of the solubility behavior of CaSO 4 in the quaternary systems CaSO 4 + H 2 SO 4 + (heavy metal)SO 4 + H 2 O over large ranges of temperature and concentration is a prerequisite. Up to now, although a large amount of solubility data has been reported in these systems, little information is available on the solubility of anhydrite, especially at salt concentrations near saturation points. In this paper, we introduce the effect of CaSO 4 in hydrometallurgical processes involving heavy metals, review published solubility data of calcium sulfate and its hydrate in relevant systems, and report our newly determined solubility results involving anhydrite in the quaternary systems CaSO 4 + H 2 SO 4 + MSO 4 + H 2 O (M = Cu,Zn,Mn) at 348.1 and 363.1 K. Based on the newly obtained data some application examples were given. On account of the complexity of the solubility phase diagram of these quaternary systems, where the calcium sulfate solubility is a function of its crystal type, temperature, compositions of sulfuric acid, and heavy metal sulfate, a complete solubility phase diagram is not available until some basic data measurement, for instance, water activity at temperatures higher than 298 K, and final modeling has been finished.