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Aim of the study: This study aims to evaluate the association between hepatitis B virus (HBV) and lymphoma and to characterize HBV-related lymphomas. The efficacy of prophylactic lamivudine on HBV reactivation was also evaluated. Methods: We compared the prevalence rate of HBV infection in 556 patients with lymphoma seen over a 4-yr period with that in a group of 4698 Singapore residents aged 18–69 who participated in the National Health Survey. Next, we compared the clinic-pathologic characteristics of HBV-positive and HBV-negative lymphoma cases. Results: The prevalence rate of HBV infection in our study was 10.3% (57/556), higher than the prevalence rate of 4.1% (192/4698) in the general population ( P ≤ 0.001). The higher prevalence was observed in both sexes and across different age groups. An association was observed for non-Hodgkin’s lymphoma (NHL) but not Hodgkin’s lymphoma. The characteristics of HBV-infected patients with lymphoma were similar to those who were HBV-uninfected in terms of age, ECOG, extra-nodal involvement, LDH level, stage, complete remission rate and overall survival. Use of prophylactic lamivudine significantly decreased the incidence of HBV reactivation (13% vs. 38%, P = 0.02) and disruption to chemotherapy (43% vs. 4%, P = 0.02), with a trend towards improved overall survival. Conclusions: Our findings suggest that an association exists between HBV infection and NHL. However, HBV infection does not appear to have a significant impact on the clinical characteristics and prognosis of NHL. Prophylactic lamivudine should be considered in all HBV-infected patients receiving antracycline and/or steroid containing chemotherapy. [ABSTRACT FROM AUTHOR]