The orf virus is the causal agent of contagious ecthyma in goats and sheep. The infection can be transmitted to humans and represents a typical example of occupational zoonosis. In Italy, the incidence of human infection remains uncertain because the disease is rarely reported or diagnosed. In this paper, we report a case of human orf virus infection and the laboratory methods of diagnosis. We demonstrated a genomic identity between the conserved and the variable regions of the genome of the viral strains isolated from the human patient and from the infected sheep confirming that there is no specific clone infecting humans rather than animals.