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Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma. AIM: To analyze contrast-enhanced ultrasound (CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma (HEHE) in comparison to other multilocular benign focal liver lesions (FLL). METHODS: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus. RESULTS: HEHE manifested as a single (n = 3) or multinodular (n = 22) FLL. On CEUS, HEHE showed rim-like (18/25, 72%) or heterogeneous hyperenhancement (7/25, 28%) in the arterial phase and hypoenhancement (25/25, 100%) in the portal venous and late phases (PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas (18/25, 72%); in seven patients (7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature (P < 0.01). CONCLUSION: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE.