AIMS: After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML. METHODS AND RESULTS: A 70-year-old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC-3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal-like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB-45, NKIC-3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease. CONCLUSIONS: This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.