The objective of this study was to describe the prevalence of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in a cohort of immigrants living in Palermo, Sicily. The study was carried out in the period May 2006-June 2010 and recruited a total of 393 patients (59.8% males-median age of 32.6 years). All patients were tested for serological markers of HBV, HCV, and HIV infection. One-hundred thirty-eight (35.1%) individuals did not show any HBV/HCV/HIV serological marker, while 186 (47.3%) were indicative of past or current HBV infection. A total of 42 (10.7%) subjects were HBsAg positive, 59 (15.0%) showed the serological profile "anti-HBc alone", and only 40 (10.1%) were anti-HBs alone. Overall, 22/393 (5.6%) immigrants were anti-HCV positive and 13/327 (4.0%) were infected with HIV. Findings from this study suggest that a suitable screening protocol for the viral blood/sexually transmissible diseases is recommended on entering Italy, and the adoption of health control strategies should also be considered to safeguard the health of the local population.