The Iberian, Italian or Balkan peninsulas have been considered as refugia for numerous mammalian species in response to Quaternary climatic fluctuations in Europe. In addition to this 'southerly refugial model', northern refugia have also been described notably for generalist and cold-tolerant species. Here, we investigated the phylogeographic pattern of the weasel (Mustela nivalis) to assess the impact of Quaternary glaciations on the genetic structure, number and location of refugia as well as to determine the impact of human movements on the colonization of Mediterranean islands. We sequenced 1690 bp from the mitochondrial control region and cytochrome b for 88 weasels distributed throughout the western-Palaearctic region, including five Mediterranean islands. Phylogenetic analyses of combined genes produced a clear phylogeographic pattern with two main lineages. The first lineage included all of the western-continental samples (from Spain to Finland) and shows low levels of genetic structure. Demographic analysis highlighted several characteristics of an expanding group, dated approximately at 116 kiloyears (kyr; Riss glaciation). The genetic pattern suggested a northeastern-European origin from which colonization of southwestern Europe took place. The second lineage was divided into five subgroups and indicated a common origin of insular and Moroccan samples from eastern Europe. Eastern-continental weasels did not exhibit signs of sudden expansion, suggesting stable population size during the last ice ages. The time of expansion of Sicilian and Corsican populations was dated around 10 kyr ago, which supports the hypothesis of an early human intervention in the colonization of Mediterranean islands.