The assessment of the environmental quality of coastal lagoons is rather difficult as their intrinsic high variability limits the power of analytical chemistry and ecotoxicological approaches. Aim of the present work was to integrate geochemical and biological data which were simultaneously collected from the Pialassa Baiona lagoon (Ravenna, Italy), and evaluate the usefulness of a biomonitoring strategy based on sentinel organisms and biomarkers. Geochemical analysis on suspended, surface, and subsurface sediments were performed at five different sites of the lagoon; moreover the heavy metal bioaccumulation and a battery of biomarkers was evaluated in Mytilus galloprovincialis transplanted in the same sites. Heavy metals appeared to be diffused throughout the lagoon reaching higher levels in the southernmost sites, and mainly concentrated in suspended sediments. Lysosome membrane stability, neutral lipid and lipofuscin accumulation, and metallothionein levels in mussels indicated the development of a stress syndrome in animals exposed to the polluted sites.