A new method has been developed that predicts the natural background concentrations of microelements of interest in sediments using the concentrations of various components present in the sample. This is done by developing multiple linear regressions using a dataset which has been selected, using radiochronological dating and statistical methods, to reflect the concentration distributions of natural levels of a large number of sediment constituents. This method is demonstrated in Venice Lagoon, using data generated in a lagoon-wide sampling effort. A quantitative assessment is carried out of the variability of natural background levels at the lagoon scale for the main inorganic microelements, and distribution maps of the background and anthropogenic concentrations of a selected metal (Ni) in sediments at the lagoon scale are presented. With sufficient data, this method can be applied in other areas, allowing for a site-specific separation of natural background and anthropogenic levels of microconstituents in sediments, providing insights into regional geochemistry and aiding in the risk-based management of coastal sediments.