Veno-occlusive disease (VOD) of the liver is a severe complication of high-dose chemotherapy and allogeneic or autologous stem cell transplantation with potential fatal outcome. We report a case of severe VOD in a patient with a high-grade B-cell lymphoma. Liver-venule occlusion was confirmed by liver biopsy. Supportive care, fibrinolytic treatment with recombinant tissue plasminogen activator and defibrotide maintenance therapy led to complete resolution of VOD demonstrated at liver biopsy and with a follow-up of 44 months after autologous peripheral blood stem cell transplantation. The literature on VOD has been reviewed.