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Stable isotopes in mollusc shells, together with variable growth rates and other geochemical properties, can register different environmental clues, including seawater temperature, salinity and primary productivity. However, the strict biological control over the construction of biominerals exerted by many calcifying organisms can constrain the use of these organisms for paleoenvironmental reconstructions. Biologically controlled calcification is responsible for the so called vital effects that cause a departure from isotopic equilibrium during shell formation, resulting in lower shell oxygen and carbon compared to the equilibrium value. We investigated shell oxygen and carbon isotopic composition of the bivalve Chamelea gallina in six sites along with a latitudinal gradient on the Adriatic Sea (NE Mediterranean Sea). Seawater δ18O and δ13CDIC varied from North to South, reflecting variations in seawater temperature, salinity, and chlorophyll concentration among sites. Shell δ18O and δ13C differed among sites and exhibited a wide range of values along with the ~400 km latitudinal gradient, away from isotopic equilibrium for both isotopes. These results hampered the utilization of this bivalve as a proxy for environmental reconstructions, in spite of C. gallina showing promise as a warm temperature proxy. Rigorous calibration studies with a precise insight of environment and shell growth are crucial prior to considering this bivalve as a reliable paleoclimatic archive. [ABSTRACT FROM AUTHOR]