Background: Hepatitis B virus (HBV) reactivation during chemotherapy may lead to disruption of chemotherapy, hospitalization for hepatitis, or even death. Prophylactic therapy with lamivudine (LAM) has been shown to prevent HBV reactivation. However, screening for HBV is uncommon in practice, and it remains unclear whether its benefits will outweigh its costs and inconvenience. Methods: A decision analytic model was developed for patients with lymphoma to compare the clinical outcomes and costs over a 1-year horizon of 3 strategies for HBV screening prior to R-CHOP chemotherapy: (1) screen all patients for HBsAg (All), (2) screen patients identified as being high risk for HBV infection (HR), and (3) screen no one (None). Patients testing positive were given LAM until 6 months following completion of chemotherapy. Those not screened were initiated on LAM only when HBV hepatitis occurred. Risks for HBV hepatitis, recovery, HBV-related death, and lymphoma outcomes were derived from systematic literature review from 1997-2009. A third-party direct payer perspective in 2010 Canadian dollars was used. Results: See table. Screening all patients was the dominant strategy. It was both least costly and most effective in increasing the 1-year survival rate. This is likely because it reduced both hospitalization and death from HBV-related hepatitis, which are associated with considerable cost. The analysis was sensitive to the cost of HBsAg testing, the prevalence of HBsAg positivity in both the high risk and low risk groups, and the effectiveness of LAM in preventing reactivation. Conclusions: In patients receiving CHOP-R for lymphoma, screening all patients for HBV is more clinically effective and less costly than screening only high-risk patients or screening no patients. Further study is needed to examine the cost-effectiveness of screening of HBV in other settings.