OBJECTIVES:  To estimate the health care resource utilization (HRU) and cost associated with newly diagnosed mesothelioma, a rare and deadly disease with limited treatment options, compared to Medicare beneficiaries without cancer. METHODS:  Using data from SEER-Medicare, we describe HRU and costs for Medicare patients diagnosed with mesothelioma between 2008 and 2009 and a matched comparison group of patients without cancer. Patients were matched on age, sex, comorbidity index, race and SEER region, and were followed through 2010. The proportion of mesothelioma patients using each type of health care service within the study observation was compared to the matched sample using chi-square tests. A t-test and a non-parametric test (Wilcoxon-Mann-Whitney) were used to compare continuous cost variables. RESULTS:  We identified 175 mesothelioma patients and 350 comparison subjects who were enrolled in Medicare Parts A, B, and D, and were not HMO members. Nearly all aspects of HRU that we examined, including inpatient hospitalization (92% of mesothelioma patients had an inpatient hospitalization versus 20% of comparisons; p<0.001), outpatient hospitalization (89% versus 61%; p<0.001), emergency room visit (41% versus 22%; p<0.001), physician office visit (98% versus 93%; p<0.001), hospice (52% versus 0.3%; p<0.001), use of durable medical equipment (56% versus 28%; p<0.001), and home health care (41% versus 10%; p<0.001), as well as actual mean costs for the total observation period associated with HRU (except pharmacy) ($US 66,659 versus $US 12,911; p<0.001) are higher in mesothelioma patients compared to matched comparisons without mesothelioma. Pharmacy use was similar between the groups (97% versus 94%, p=0.2551), and costs were higher for the comparison group ($US 1,917 versus $US 2,725; p<0.001). CONCLUSIONS: Mesothelioma- associated medical resource utilization and associated expenditures are substantive, and similar to other cancers. In order to reduce the burden of illness associated with mesothelioma, continued efforts in the development of more efficacious treatments are needed.