This study estimated the average lifetime costs of patients with chronic lymphocytic leukemia (CLL) relative to similar patients without cancer. An analysis of the Medicare 5% database (1999-2007) was conducted. Each patient with CLL was matched up to three patients without cancer based on year of birth, gender, race and state. Average total lifetime costs were estimated using the Kaplan-Meier sample average estimator and stratified by treatments. For patients who died, average monthly costs during continuing and terminal phases were compared between cohorts. A total of 7463 patients with CLL and 22 331 matched controls were identified (mean age: 76 years; proportion of women: 49%). The mean observation period was 39.4 months for patients with CLL and 45.9 months for matched controls. Patients with CLL incurred average costs of $87,151 compared to $47 642 for matched controls (p < 0.001). Among common CLL treatments, average costs per patient were $5140 for rituximab and $953 for radiation therapy. Compared to matched controls, patients with CLL had significantly higher monthly costs during the continuing and terminal phases. This study showed that average lifetime costs to Medicare were $87,151 for patients with CLL compared to $47,642 for matched controls without cancer, for a significant difference of $39,509.