In Italy, the HIV-1 epidemic is still mainly sustained by the subtype B genetic form, although other and novel subtypes and circulating recombinant forms (CRFs) have been reported. A total of 215 HIV-1 pol gene sequences were collected between 1992 and 2010. Multiple alignments spanning subtype-specific HIV-1 B pol sequences were analyzed by Bayesian phylogenetic methods. Subtype B represented 90.7% (n=195) of the sequences. Three main clusters were detected. The root of the tree dated to 1987. Most of the observed viral gene flow events occurred from heterosexual to intravenous drug users (IDUs). Phylogenetic and molecular clock analysis showed an early HIV-1 subtype B introduction in the mid-1980s and dissemination within local risk-specific clusters. This is the first study to describe in detail the HIV-1 molecular epidemiology in one of the largest islands in the European basin. The future potential of the Sardinian epidemic as a hub between Southern and Northern Europe has to been considered.