In this study, a biogeochemical model of the mercury cycle is applied to the Marano-Grado Lagoon (North Adriatic Sea, Italy) to (1) integrate the ensemble of disconnected and snap shot measurements collected over the last decade into a common and coherent framework, (2) assess the concentration of mercury species (HgII, MeHg, Hg0) in water, sediment and particulates, and (3) quantify the mercury fluxes and budgets within the lagoon and among the lagoon, the atmosphere and the Adriatic Sea. As a result of long-term industrial and natural contamination, the Marano-Grado Lagoon is a hot spot of mercury contamination in the Mediterranean Region. Several monitoring activities have been undertaken to evaluate the environmental impacts and to better understand mercury cycling in this region. We used the results from these studies to build a mercury biogeochemical model and assess its ability to accurate predict mercury concentrations and fluxes. The results indicate that 1) the lagoon is a contaminated site, with water and sediment concentrations of Hg and MeHg higher than those of comparable environments; 2) there is substantial production of MeHg favored high productivity, occurrence of seasonal anoxia, and shallow conditions; and 3) the lagoon is a source of mercury contamination for the Mediterranean Sea, contributing to about 5% of the total HgT load. Research also indicates that the most critical shortcoming of the currently available data sets is the lack of complete synoptic measurements, even for short time periods. Future research programs must also include information on the photo-transformation rates, such as of photo-reduction, photo-oxidation and photo-demethylation.