We investigated the effectiveness of lamivudine to prevent hepatitis flare up due to reactivation of hepatitis-B virus (HBV) in hepatitis-B surface antigen (HBsAg)-positive patients with Non-Hodgkin's lymphoma (NHL) during cytotoxic chemotherapy. HBsAg-positive patients with NHL were identified from the lymphoma database of the Asan Medical Center from January 1995 to August 2002, and their medical records were reviewed. We found that 31 patients were received cytotoxic chemotherapy among 41 NHL patients with HBsAg-positive during same period. We divided them into 2 groups of HBsAg patients with NHL as follows: Group A who received cytotoxic chemotherapy with lamivudine 100 mg daily; Group B without any prophylactic antiviral therapy. There were no significant differences between Group A and B in several clinical variables. Seventeen patients (85%) in group B and one patient (9%) in Group A had hepatitis due to reactivation of HBV (p<0.001), with one hepatic failure related death in Group B and none in group A. The mean dose intensity of adriamycin actually delivered was 13.3 mg/m²/week (80% Relative Dose intensity (RDI)) in Group A and 9.1 mg/m²/week (55% RDI) in Groups B (p<0.001). Our data suggest that the frequency of chemotherapy-related HBV reactivation may be significantly decreased by lamivudine prophylaxis with maintenance of the dosage of adriamycin.