To analyze the results of ultrasound (US)-guided biopsy as a predictor of the outcome of interventional treatment of hepatocellular carcinoma (HCC). US-guided biopsy was performed in 125 lesions in 102 high-risk patients, before transcatheter arterial embolization (TAE) (82 lesions) or before percutaneous ethanol injection (PEI) therapy (25 lesions, including 14 lesions previously treated with TAE). Pathologic results were correlated with treatment effects. Results of biopsy confirmed 107 HCCs, which were classified as early (n = 17), frank (n = 67), sclerosing (n = 12), or poorly differentiated or undifferentiated (n = 11). Hypervascularity was observed in most frank HCCs, with a good response to TAE. Tumor vascularity in early or sclerosing HCCs was slight and did not respond to TAE. Sclerosing and poorly differentiated or undifferentiated HCCs enlarged after treatment, whereas early HCCs did not. Early HCCs were treated successfully with PEI therapy; sclerosing HCCs responded poorly to PEI therapy. Evaluation of histologic subtype of HCC by means of US-guided biopsy is essential, because subtype may affect treatment planning.