Background & Aims: A molecular and pathological classification system for hepatocellular adenomas (HCA) was recently introduced and four major subgroups were identified. We aimed to validate this adenoma classification system and to determine the clinical relevance of the subtypes for surgical management. Methods: Paraffin fixed liver tissue slides and resection specimens of patients radiologically diagnosed as HCA were retrieved from the department of pathology. lmmunostainings included liver-fatty acid binding protein (L-FABP), serum amyloid A (SAA), C-reactive protein (CRP), glutamine synthetase (GS) and beta-catenin. Results: From 2000 to 2010,58 cases (71 lesions) were surgically resected. Fourteen lesions were diagnosed as focal nodular hyperplasia with a characteristic map-like staining pattern of GS. Inflammatory HCA expressing CRP and SAA was documented in 36 of 57 adenomas (63%). Three of these inflammatory adenomas were also beta-catenin positive as well as GS positive and only one was CRP and SAA and GS positive. We identified eleven L-FABP-negative HCA (19%) and four beta-catenin positive HCA (7%), without expression of CRP and SAA and with normal L-FABP staining, one of which was also GS positive. Six HCA were unclassifiable (11%). In three patients multiple adenomas of different subtypes were found. Conclusions: Morphology and additional immunohistochemical markers can discriminate between different types of HCA in >90% of cases and this classification, including the identification of beta-catenin positive adenomas may have important implications in the decision for surveillance or treatment. Interpretation of nuclear staining for p-catenin can be difficult due to uneven staining distribution or focal nuclear staining and additional molecular biology may be required. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.