The zebra mussel Dreissena polymorpha is widely present in Italy, but Italian populations of this bivalve have never been genetically characterized. The mitochondrial Cytochrome Oxidase subunit I gene fragments have been used to determine the genetic structures of 3 populations from Lake Garda (n = 30), the first Italian basin colonized by this species, as well as 2 populations from Lake Constance, Germany (n = 14). A Neighbor-Joining tree and a Maximum Likelihood analysis were performed with 4 new Italian (LG1-LG4) and 3 German (LC1-LC3) haplotypes, also considering all the available Dreissena sequences from GenBank in order to estimate phylogeographic relationships. Almost all Italian haplotypes clustered with German and mid-European samples providing evidences of a mixed origin for Italian mussels. We speculate about Lake Garda colonization, for which the hypothesized "German origin" has been partially confirmed as well as the necessity of more efficient control strategies at least to minimize new colonizations.