AIMS To define a new histological staging and grading system for primary biliary cirrhosis (PBC), to provide more information reflecting clinical laboratory data and the prognosis to hepatologists. METHODS AND RESULTS First, 17 histological lesions of PBC were scored in 188 needle liver biopsy specimens. Factor analysis yielded three independent groups of factors: factor 1 (fibrosis, fibrous piecemeal necrosis, orcein-positive granules, bile plugs, Mallory bodies, feathery degeneration, bile duct loss and atypical ductular proliferation); factor 2 (portal inflammation, eosinophilic infiltration, lymphoid follicles, epithelioid granulomas, interface hepatitis and chronic cholangitis); and factor 3 (interface hepatitis, lobular hepatitis, acidophilic bodies and pigmented macrophages). The eight findings of factor 1, but not factors 2 and 3, were significantly correlated with clinical laboratory data and scores in the Mayo Clinic's prognostic model. Factor 1 lesions may reflect histological progression (staging), while factor 2 and 3 lesions may relate to necroinflammatory activity (grading). Then, we devised a staging and grading system using three lesions (bile duct loss, fibrosis and orcein-positive granules) from factor 1 and three from factors 2 and 3 (chronic cholangitis, interface hepatitis and lobular hepatitis). CONCLUSION This new system might provide more pathological information on PBC patients for hepatologists.