Here we report three cases of hepatitis B virus (HBV) reactivation after cessation of preemptive lamivudine therapy in B-cell lymphoma patients treated with rituximab plus CHOP (R-CHOP). Two patients received eight cycles of R-CHOP, and one received two cycles of R-CHOP followed by two courses of rituximab. As all the patients were HBV surface antigen (HBsAg) positive, lamivudine was administered simultaneously with R-CHOP to prevent virus reactivation. All the patients developed hepatitis due to HBV reactivation 6, 8 and 13 months after completion of chemotherapy, and 4, 2 and 2 months after cessation of lamivudine, respectively. They were treated with either lamivudine or entecavir and all achieved full recovery. When HBV carriers undergo immunosuppressive anticancer treatment, prophylactic antiviral therapy is well recognized as effective. However, the optimal method of prophylaxis has not yet been established. Since the introduction of rituximab, new problems such as delayed HBV reactivation from HBsAg positive patients and de novo hepatitis B from HBsAg negative patients have emerged. Guidelines for prophylactic antiviral therapy in the era of rituximab need to be established.