Hepatocellular cancer is the third leading cause of cancer-related deaths worldwide. Its incidence has increased dramatically in the United States because of the spread of hepatitis C virus infection and is expected to increase for the next 2 decades. Hepatitis B virus, hepatitis C virus, and chronic heavy alcohol use leading to cirrhosis of the liver remain the most important causes. The diagnosis of hepatocellular cancer rests on a combination of radiologic, serologic, and histopathologic criteria. Liver transplantation is the only definitive treatment. Resection of the tumor and other percutaneous therapies are more commonly used in practice, because most hepatocellular cancers are detected at an advanced stage. Patients who are at high risk for the development of hepatocellular cancer should be screened with an ultrasound of the liver every 6 months. The prognosis is dependent on both the underlying liver function and the stage at which the tumor is diagnosed. The aim of this review is to familiarize internists in screening, diagnosis, and referral of patients with hepatocellular cancer in an appropriate and timely fashion.