OBJECTIVES: To compare long-term costs to Medicare in patients diagnosed with follicular lymphoma (FL) receiving frontline chemotherapy +/- rituximab. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims, we identified 1,117 FL patients diagnosed between 01/99 and 12/05.  Patients were included if chemotherapy began within 90 days of cancer diagnosis and consisted of CHOP (cyclophosphamide [C], doxorubicin, vincristine [V], and prednisone [P]) or CVP ± rituximab.  Monthly Medicare paid amounts were calculated for each of 48 monthly partitions following chemotherapy initiation.  To account for censoring we conducted 48 inverse probability-weighted (IPW) least-squares regression analyses to examine patient factors associated with cumulative costs after each partition.  Total costs were divided into chemotherapy and non-chemotherapy.  Overall survival was estimated using Kaplan-Meier analysis. RESULTS: The median age was 73 years, 56% were diagnosed with stage III-IV disease, 67% received rituximab, and, among these, the average cost of rituximab was $17,958 during the first 12 months of frontline therapy.  In IPW regression, the incremental cumulative total cost associated with rituximab was $20,622 (95% Confidence Interval [CI] $16,999-$24,092) at month 6, $19,606 (95% CI $14,996-$23,914) at month 12, and $18,122 (95% CI $8,110-$27,533) at month 48.  Other factors associated with higher costs were later cancer stage and higher comorbidity index.  The cumulative chemotherapy cost associated with rituximab was $18,109 (95% CI $16,081-$20,365) at month 6, $16,249 (95% CI $13,820-$19,023) at month 12, and $16,130 (95% CI $11,320-$21,015) at month 48.  There were no differences in cumulative non-chemotherapy costs associated with rituximab at any time.  Kaplan-Meier 48-month survival was 74.4% for rituximab and 62.6% for non-rituximab patients.  CONCLUSIONS: The net cost of rituximab is consistent with the cost of rituximab treatment, suggesting that over 48 months additional costs from improved survival were balanced by the reduced need for medical services.