From the beginning of October 2006 to January 31st 2008, in the context of a work sponsored by Merial Italia, a diagnostic pathway has been developed for the study of post-weaning multisystemic wasting syndrome (PMWS) of pigs. Superficial inguinal and bronchial lymph nodes, ileum, tonsil and lung from 3 to 5 subjects (229 pigs belonging to 64 farms from North and Centre Italy) were collected. The samples were valued by histological and immunohistochemical (IHC) assays for porcine circovirus-2 (PCV2). The diagnosis confirmed PMWS in those cases with inclusion bodies or where the presence of a positive IHC stain was contextual to the lesions indicative of PMWS in the lymphoid tissue (depletion and/or granulomas) and/or lung (interstitial pneumonia). In the other cases the samples were considered PCV2 infected when PCV2-positive cells were present without PMWS lesions; negative in the absence of PCV2 infection and PMWS lesions. PMWS was diagnosed on 48 farms; 21 where the total number of examined subjects had a conclusive diagnosis of PMWS, whereas the diagnosis could be considered conclusive for PMWS only for some animals on the remaining 27. The protocol proved more reliable when appled to a group of animals than to a single pig.