There are currently four needle biopsy methods for obtaining tissue from patients with possible diffuse liver disease or cancer. These include percutaneous blind needle biopsy, a visually guided needle biopsy at laparoscopy, guided fine-needle biopsies with ultrasonography or computed tomography, and the transvenous liver biopsy. We and others have found the guided fine-needle biopsy technique to be safe, relatively cheap, and highly accurate in the diagnosis of liver cancer. Blind percutaneous biopsy should be reserved for patients with possible diffuse, noncancerous, liver disease. Guided biopsies at laparoscopy can be done if the other two methods fail to give a tissue diagnosis. The transvenous approach is useful in patients with a coagulation disorder.