Canine parvovirus type-2 (CPV-2) is a DNA virus that causes a very common worldwide diffused infectious disease in dogs. Since its appearance, the CPV-2 evolved generating novel genetic and antigenic variants (CPV-2a/2b/2c) which are distributed throughout the world. In the present study, the frequency of CPV-2 in a canine population in Sicily (Italy) was investigated, using a polymerase chain reaction (PCR) for a fragment of the VP2 gene. Out of a total of 673 samples from 370 dogs, submitted to the laboratory from July 2009 to August 2015, 265 samples (39.38%) were positive and these were further analyzed by restriction fragment length polymorphism (RFLP) and DNA sequence analysis. A high prevalence of the CPV-2c variant (79.56% of CPV-2 positive dogs) was observed in this survey, underlining that this type of CPV field isolate is prevalent circulating in Sicily. Sequence and phylogenetic analysis showed a close relationship with CPV-2a and CPV-2c strains from Europe and non-European countries. Considering that CPV-2c is reaching a worldwide distribution and that this variant is also affecting vaccinated dogs, efforts should be made towards the development of new CPV vaccines.