Low Grade Non-Hodgkin s Lymphoma (LGNHL) is an indolent form of NHL with a median survival of four to eleven years. This survival is dependent on the responsiveness to therapy and the number of disease relapses. After multiple relapses, this lymphoma becomes refractory to standard therapies. Thus the median survival is dramatically shortened to 24 to 26 months. Relapsed, refractory low-grade lymphoma (RRLGNHL) is a common disease progression and the focus of multiple studies in the search for more effective therapies. Rituximab is an anti-CD20 immunotherapy approved for the treatment of RRLGNHL. It is marginally more effective in refractory cases than salvage therapy, but has a less severe side effect profile. OBJECTIVE: To estimate the cost-effectiveness ratio of rituximab in the treatment of RRLGNHL. METHODS: The study utilized a societal perspective with a two-year time horizon and an annual discount rate of 3%. Outcomes data and their probabilities were abstracted from randomized controlled trials for rituximab and DHAP in RRLGNHL patient populations. Direct medical costs, drug costs and health-state related utilities were abstracted from other studies, standard Medicare reimbursement rates and the Red Book. An incremental cost-effectiveness ratio (ICE) was used to estimate the effectiveness of rituximab compared to DHAP. RESULTS: The study found an ICE ratio of $58,166 per quality adjusted life-year saved. The model was found to be sensitive to the medication costs, medication response rates and the cost of autologous bone marrow transplantation. CONCLUSION: Based on the findings, rituximab appears to be a marginally cost-effective alternative for RRLGNHL. Relative drug costs and response rates must be considered before a conclusion can be drawn for a specific institution.