Patients in hematology units are at risk of hepatitis C virus infection. In these patients acute infection is reportedly mild, presents only moderately increased ALT levels, is characterized by a significant delay in anti-HCV seroconversion and does not influence the course of the underlying disease. We describe two fatal cases of acute HCV infection occurring in patients with hematologic malignancies and we hypothesize that, in a subset of immunocompromised patients, acute HCV infection may play a still unrecognized but not marginal role in contributing to death. Prospective studies are needed to define the frequency of fatal acute HCV infection among hematologic patients undergoing chemotherapy.