The Parapoxvirus (PPV) genus of the Poxviridae family includes four worldwide-distributed viral species that mainly infect domestic and wild ruminants (e.g., sheep, goat, and cattle). PPV species are transmissible to humans and, for this reason, are considered zoonotic agents of veterinary and public health relevance [1,2]. The fact that PPV infection has been reported in an even broader host range (including camels, seals, and deer species) highlights the emerging importance of this genus [1,3,4]. PPVs are epitheliotropic viruses whose clinical manifestations include exanthematic lesions as painful pustules and vesicles. Clinical diagnosis of PPV infection is often made difcult by both the absence of pathognomonic signs and the great similarity in the symptoms to either different Poxviridae infections or unrelated exanthematic diseases, such as cutaneous anthrax, foot-and-mouth disease, blue tongue, and bovine viral diarrhea. In addition, subclinical infections have been recorded. Thus, improvement of molecular analyses and epidemiological studies is considered an urgent priority in order not only to avoid unnecessary treatment due to misdiagnosis but also to lessen the economical impact of PPV diseases and to implement strategies for the limitation of this infection. Clinical evidence and restriction analysis have been traditionally used to diagnose and
characterize PPV diseases. Nevertheless, the historical relevance of the Poxviridae family has increased the availability of genomic data in scientic databases. This further facilitates the use of the molecular diagnostic approach for improved diagnosis of PPV infection.