During a 4-year period portal vein thrombosis was diagnosed in 20 Child class A patients with cirrhosis by means of ultrasound and ultrasound-Doppler study. Seventeen of them showed single or multiple focal liver lesions diagnosed as hepatocellular carcinoma by ultrasound-guided fine-needle biopsy and the remaining three a coarse liver echo-pattern without focal lesions. One patient was found to have developed portal vein thrombosis after the fifth ethanol injection of a single hepatocellular carcinoma lesion 17 mm in diameter. Ultrasound-guided fine-needle biopsy of the thrombus was performed on all the patients: portal vein thrombosis was neoplastic in 13 cases and non-neoplastic in seven cases (five patients with a single lesion; one with two lesions; one with coarse liver echo-pattern). Among the five patients with a single lesion, one had already been treated by percutaneous ethanol injection therapy. There were no complications related to the biopsy procedures. The diagnosis of non-neoplastic thrombosis allowed five new patients to be recruited for percutaneous ethanol injection treatment and allowed it to continue in the patient with portal vein thrombosis occurring after the fifth ethanol injection. The routine use of ultrasound-guided fine-needle biopsy of portal vein thrombosis yields an accurate diagnosis of the nature of the thrombus and can improve the selection for percutaneous ethanol injection treatment of patients with cirrhosis with hepatocellular carcinoma lesions.