AIM: To assess the ability of 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) to differentiate between benign and malignant portal vein thrombosis in hepatocellular carcinoma (HCC) patients. METHODS: Five consecutive patients who had HBV cirrhosis, biopsy-proven HCC, and thrombosis of the main portal vein and/or left/right portal vein on ultrasound (US), computer tomography (CT) or magnetic resonance imaging (MRI) were studied with 18F-FDG PET/CT. The presence or absence of a highly metabolic thrombus on 18F-FDG PET/CT was considered diagnostic for malignant or benign portal vein thrombosis, respectively. All patients were followed-up monthly with US, CT or MRI. Shrinkage of the thrombus or recanalization of the vessels on US, CT or MRI during follow-up was considered to be definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered to be consistent with malignancy 18F-FDG PET/CT, and US, CT or MRI results were compared. RESULTS: Follow-up (1 to 10 mo) showed signs of malignant thrombosis in 4 of the 5 patients. US, CT or MRI produced a true-positive result for malignancy in 4of the patients, and a false-positive result in 1.18F-FDG PET/CT showed a highly metabolic thrombus in 4 of the 5 patients.18F-FDG PET/CT achieved a true-positive result in all 4 of these patients, and a true-negative result in the other patient. No false-positive result was observed using 18F-FDG PET/CT.CONCLUSION: 18F-FDG PET/CT may be helpful in discriminating between benign and malignant portal vein thrombi. Patients may benefit from 18F-FDG PET/OT when portal vein thrombi can not be diagnosed exactly by US, CT or MRI.