The expansion of Mus musculus domesticus from its origin has been studied in detail. The coloni-zation routes and times depended on its commensal habits which favoured a rapid and recent dispersal, making it difficult to unravel the expansion pattern. The situation is still obscure in the central Mediterranean area. Mitochondrial D-loop was sequenced for 65 mice from the Aeolian Archipelago and the sixteen haplo-types identified were compared with the 528 available mouse haplotypes. The central Mediterranean phyloge-ography, the demographic history of the Aeolian mice and the relationships between mtDNA and karyotypes was investigate. Five lineages are present, belonging to five of the haplogroups previously described for the Mediterranean basin, and most individuals fall within the European haplogroups. The Archipelago was sub-jected to multiple colonizations and chromosomal and molecular data agree in indicating Sicily and Italy as possible sources of colonization in recent times. Nev-ertheless, the signatures of earlier colonizations might have been lost through extinction and admixing of mice due to human movements. Drastic events during the entire colonization process have led to the present-day random distribution of haplotypes. Furthermore, Salina emerges as an ancestral condition and no relation between karyotype composition and haplotype variabil-ity was highlighted.