This paper describes the results of the molecular and phylogenetic analysis of seven highly pathogenic avian influenza (HPAI) H5N1 strains isolated in 2006 (n = 5) and 2007 (n = 2) from wild birds and poultry in Poland. The whole genome sequence of these isolates was determined. All of the isolates possessed the hemagglutinin (HA) cleavage site sequence PQGERRRKKR*GLF typical of HPAI. Molecular markers associated with increased adaptation and virulence in mammals, as well as susceptibility to neuraminidase inhibitors, were revealed in the HA, neuraminidase (NA), and PB2 proteins. Based on the sequencing results related to the HA and NA genomic segments, H5N1 viruses circulating in Poland all belong to lineage 2.2. However, isolates isolated in 2006 were genetically distinct from those isolated in 2007 and grouped in different sublineages. H5N1 viruses isolated from wild birds in 2006 are almost identical to each other (99.9% HA; 99.6%-100% NA), and they are grouped within a cluster of viruses isolated in Germany from wild and domestic birds and mammals in 2006. Isolates from 2007 are also closely related to each other (nucleotide homologies 99.9% and 100% for HA and NA, respectively), and they are grouped together with isolates from wild and domestic birds collected in Eastern and Central Europe (Romania, Germany), and the Middle East (Kuwait, Saudi Arabia). Phylogenetic analysis of the sequences related to the internal proteins confirmed the results obtained for the HA and NA genes. Overall, the results indicate that HPAI H5N1 in Poland in 2006-07 was caused by at least two separate incursions of genetically distinct viruses.