The optimal therapy for HCV-related chronic hepatitis is the combination of pegylated interferon alpha (peg-IFN alpha) plus ribavirin (RBV). Unfortunately, both peg-IFN alpha and RBV are responsible for a wide range of adverse events and potentially severe toxicities, particularly hematological alterations. Indeed, RBV is generally responsible for anemia through hemolysis, while peg-IFN alpha induces more commonly leukopoenia and thrombocytopenia, presumably through bone marrow toxicity. Actually, data regarding histopathological bone marrow alterations in HCV-infected patients following IFN-alpha therapy is scanty. We report a case of a HCV-infected cirrhotic patient, who developed bone marrow alterations following one-year peg-IFN alpha plus RBV treatment, and we describe the associated histopathological features. Our case report provides new significant insight on the histopathological changes occurring in bone marrow of HCV-infected cirrhotic patients during peg-IFN alpha-2a plus RBV treatment, providing also additional information on potential bone marrow toxicity in the course of IFN-based treatments.