The evolution of the molluscan biota in Sabaudia Lake (Italy, central Tyrrhenian Sea) in the last century is hereby traced on the basis of bibliography, museum type materials, and field samplings carried out from April 2009 to September 2011. Biological assessments revealed clearly distinct phases, elucidating the definitive shift of this human-induced coastal lake from a freshwater to a marine-influenced lagoon ecosystem. Records of marine subfossil taxa suggest that previous accommodations to these environmental features have already occurred in the past, in agreement with historical evidence. Faunal and ecological insights are offered for its current malacofauna, and special emphasis is given to alien species. Within this framework, Mytilodonta Coen, 1936, Mytilodonta paulae Coen, 1936 and Rissoa paulae Coen in Brunelli and Cannicci, 1940 are also considered new synonyms of Mytilaster Monterosato, 1884, Mytilaster marioni (Locard, 1889) and Rissoa membranacea (J. Adams, 1800). Finally, human-driven environmental changes and cumulative anthropogenic pressures proved to be the whole driver of the constitution of the human-induced malacofauna studied, casting doubts on the correct use of the definition of “native fauna”.