This paper provides a critical analysis of archaeological small mammal collections in the Mediterranean area, from the Late Glacial to the first centuries AD, to validate the presence/absence of the house mouse through zooarchaeological criteria. The results have been synthesized through a diachronic map, whose chronological phases are related to socioeconomic and cultural human evolution. The house mouse (Mus musculus domesticus) progression in the Mediterranean begins with a quick but limited diffusion in the Eastern Mediterranean Basin achieved around the 8th millennium BC. Until the 1st millennium BC, the invasive process seems to have stopped or drastically slowed, despite the increasing opportunities of passive transport during the Bronze Age. During the 1st millennium BC, there was mass colonization by the house mouse of the entire Western Mediterranean Basin and Northern Europe. We propose to explain this chronological gap in the colonization of the Eastern and Western Mediterranean using source-sink theory considering that the western environments acted like sinks until the first millennium BC. At that time the Western Mediterranean was fully opened to Eastern influences and migrations, and the human pressures on the environment drastically increased. This may have favoured definitively the adaptation of the house mouse to the Western commensal niches.