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Extensive screening analyses of perfluorooctane sulfonate and related perfluorinated compounds (PFCs) in biota samples from all over the world have identified PFCs as global pollutants and have shown their bioaccumulation into higher trophic levels in the food chain. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmental contaminants belonging to a chemical group known as perfluorinated compounds. PFOS and PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters. The United States Environmental Protection Agency (USEPA) considers both compounds to be carcinogenic and the European Food Safety Authority (EFSA) recently pointed out that they are associated with adverse health effects. Diet is considered the main source of exposure to PFCs, which have been found more frequently in fish and other seafood, compared to other food groups. In fact, aquatic ecosystems represent the final reservoir for PFCs due to their great affinity for sedimentary and living organic matter. In these systems, measured levels of persistent organic pollutants (POPs) could increase along the trophic web, ultimately affecting humans that consume aquatic species. In this study, PFOS and PFOA was detected by LC-MS/MS in muscle samples of Coregonus lavaretus (European whitefish) and Perca fluviatilis (European perch) collected from Lake Maggiore, a large lake located on the south side of the Italian Alps. PFOA was not found in any of the investigated samples above the limit of quantitation of 0.50ngg−1 fresh weight (fw), whereas PFOS was detected in all 90 samples with concentrations of up to 46.0ngg−1fw. Mean concentrations were 22.2ngg−1fw in P. fluviatilis and 20.0ngg−1fw in C.lavaretus. Comparison of our results with literature data on PFOS intake suggested that fish from Lake Maggiore may be a significant source of dietary PFOS exposure, even if the reported values were lower than the Total Daily Intake (TDI) proposed by EFSA. [ABSTRACT FROM AUTHOR]