Masses that occur in the liver can be determined to be harmless (benign) or malignant (cancerous) in various ways. The first, involves the use of imaging techniques such as Computed Axial Tomography (CT) scan / Magnetic Resonance Imaging (MRI) or the injection of a dye into the blood vessels (angiography). The larger the liver cancer the more likely these imaging techniques will be able to diagnose it. Liver cancer has special features, such as a rich blood supply or tendency to increase in size, which these imaging techniques can detect.

If imaging can not determine if a tumor is benign or malignant, a fine needle biopsy may be performed. In this procedure, a fine (very thin) needle is passed through the skin, into the liver and directed toward the tumor using an exterior ultrasound to guide the needle.

If a needle biopsy is performed, Johns Hopkins' pathologists, Drs. Robert Anders, Michael Torbenson, John Boitnott all have focused interest on interpreting these biopsies. The normal liver cells grow in columns that are one or two cells thick. In liver cancer, the columns of liver cells become wider than one or two cells. The wide columns of liver cells can be seen on microscopic examination and are one helpful feature of liver cancer.