The clinical and pathomorphological patterns of parvovirus B19 (PVB19)-associated diseases is the result of a balance between virus, host target cells and immune response. It is a characteristic feature of PVB19 that in patients with various other preexisting diseases, e.g., many hemolytic anemias, immune complex-mediated vasculitic disorders, and primary or secondary immunodeficiencies, the underlying diseases can be triggered, aggravated or complicated by severe organ manifestations. Identification of PVB19 by means of routine histology and immunohistology is only given in lytic infections occurring in transient aplastic anemia or nonimmune hydrops fetalis by the detection of viral inclusion bodies in erythroid precursor cells. In all other PVB19-associated diseases, molecular pathological methods must be applied. In this report, quantitative real-time polymerase chain reaction was used to determine the viral load in formalin-fixed and paraffin-embedded tissues derived from various organs. Using in situ hybridization it was demonstrated that endothelial cells of the microcirculatory periphery of the heart and hepatobiliar system in lytic infections are PVB19-specific target cells in children and adults. Because treatment of lytic PVB19 infection has been successfully applied, the pathologist should be alerted to include PVB19 into the diagnostic spectrum of viral disease, especially in immunocompromised patients.