Hepatic angiomyolipoma (AML) is frequently misdiagnosed. HMB-45 is a promising immunomarker for this tumor that leads to recognition of some AMLs with unusual morphology. The purpose of this collaborative study is to better define the morphologic variations of AML. Thirty AMLs were examined, including four biopsy specimens and two fine-needle aspirates. The diagnosis was confirmed by the presence of HMB-45-positive myoid cells. Almost half the cases were originally misdiagnosed as carcinomas or sarcomas. There was marked female predominance (25:5), and the mean age was 48.7 years (range 29-68). Three patients (10%) had evidence of tuberous sclerosis and all had renal AML. According to the line of differentiation and predominance of tissue components, the tumors was subcategorized into mixed, lipomatous (> or = 70% fat), myomatous (< or = 10% fat), and angiomatous type. The mixed type was the most common (11 resected cases), comprising sheets of epithelioid muscle cells admixed with islands of adipocytes, abnormal vessels, and frequently, hematopoietic cells. Six tumors (including three from biopsy specimens) were heavily fatty and showed predominantly adipocytes with epithelioid and short spindle myoid cells webbed between fat cells. Of 10 myomatous AMLs, five tumors showed a pure sinusoidal trabecular pattern and comprised mainly epithelioid cells. Typically, mature adipocytes were absent or scanty, but fat was seen as fine droplets within cytoplasm or as occasional large globules in sinusoids. Pelioid and inflammatory pseudotumor-like patterns were identified focally. Regarding cellular features of the myoid cells, most of the epithelioid cells were either eosinophilic or clear with spiderweb cell morphology. Three AMLs showed an almost purely oncocytic appearance with scanty fat. Large pleomorphic epithelioid cells existed as small foci. Spindle cells arranged in long fascicles were uncommon. D-PAS-positive globules were common around pelioid areas. Brown pigments with staining characteristics of hemosiderin and/or melanin were noted. In conclusion, we propose HMB-45-positive myoid cells as the defining criterion of hepatic AML, which is a tumor capable of dual myomatous and lipomatous differentiation and melanogenesis. Because of its protean morphologic appearance, recognition of the various variant patterns and cell types is important for a correct diagnosis, assisted by immunohistochemical confirmation with HMB-45. Trabecular and oncocytic cell tumors appear to stand out as distinctive subtypes.