In situ hybridization and immunohistochemistry with different types of antibody (monoclonal vs. polyclonal, natural vs. synthetic) was compared to detect porcine circovirus 2 (PCV2) in formalin-fixed, paraffin-embedded tissues from pigs with experimentally and naturally occurring postweaning multisystemic wasting syndrome. PCV2 DNA and antigen was detected in tissues from both experimentally and naturally infected pigs by in situ hybridization and immunohistochemistry, respectively. Statistical evaluation revealed that more PCV2 positive signals were significantly detected in both experimentally and naturally infected pigs by in situ hybridization compared with immunohistochemistry (P<0.05). The results of this study demonstrated that in situ hybridization proved more sensitive than immunohistochemistry for the detection of PCV2 in formalin-fixed, paraffin-embedded lymph node tissues.