The evidence for HLA-Cw antigens' involvement in the modulation of the immune response in bone marrow transplantation, NK alloreactivity and the susceptibility and follow-up for different diseases has been growing in the recent years, but very few data on HLA-Cw distribution in healthy Italian subjects are available to date. This report presents an updated description of HLA-Cw frequencies in Italy, comparing data from the northern (Lombardia) and southern (Campania and Puglia) parts of the country. A total of 1101 healthy subjects of Italian origin were genotyped, and the results showed that HLA-Cw*04, Cw*07, Cw*12, and, in particular, Cw*0401, Cw*0701, Cw*1203, were the most frequent alleles found in all three regions analysed. Nevertheless, statistically significant differences were observed in Cw*07 distribution, which was more frequent in the southern than in the northern part of Italy (28.8% vs 22.4%; p=0.001; OR: 1.4; 95%CI: 1.14-1.73), and in Cw*12 distribution, which was more frequent in the north than the south (17.0% vs 12.4%; p=0.007, OR: 1.4; 95%CI: 1.10-1.91). These results, which give an improved pattern of distribution of HLA-Cw alleles in the Italian population, would be useful in bone marrow transplantation and anthropological studies. Moreover, due to the important role of HLA-Cw antigens in modulation of the immune response and NK alloreactivity, these data would be of interest in studies on susceptibility, follow-up and/or protection against different diseases.