Canine parvovirus type 2 (CPV2) emerged for the first time in 1978 and evolved into two antigenic variants CPV2a and CPV2b and the third new antigenic variant CPV2c reported in 2000 in Italy. During 2014 unexplained outbreaks of gastroenteritis were observed in kennels where an extensive vaccination program was ongoing and where vaccinated animals showed pathologic lesions consistent with typical parvovirosis. The aim of this study was to investigate whether CPV2 could have played a role in the emergence of these cases and to evaluate genetic or pathological specificities of the virus and the disease. Using PCR and phylogenetic analysis we showed that the CPV2c variant is circulating in Croatia and is in close relationships with isolates from North and South America. Histopathological lesions and cell tropism that are known for CPV2 we are reporting the identification of the virus in glial cells and ovaries. It seems that evolution of CPV and CPV2a-c and adaptation to dogs are two independent events. Croatian isolates had specific and some unique amino acid mutations under positive selection. The effect of the alterations on the immunoglobulin binding cannot be excluded.