Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, affecting 175 million people globally. Over 80% of acutely infected patients go on to develop chronicity, but only 20% to 25% will develop end-stage liver disease and its complications. The sequelae of HCV-induced chronic liver disease accounts for 8,000 to 10,000 deaths annually in the United States and is currently the leading indication for liver transplantation. To date, there are no accurate noninvasive markers of disease activity and fibrosis. Liver biopsy is indicated to exclude other forms of liver pathologies and to establish the stage of liver disease. In this study, the role of liver biopsy in chronic hepatitis C was evaluated. Additionally, we calculated a discriminant score to predict cirrhosis in chronic hepatitis C infection. Our results showed that additional diagnoses or unsuspected diagnoses are less frequent than clinicians' suspected. We confirmed that the discriminant score for predicting cirrhosis is inferior to liver biopsy. In conclusion, the majority of patients with chronic hepatitis C will require a liver biopsy, which has an important implication on staging of the liver disease, prognosis, and possibly further management options.