Renal cell carcinoma (RCC) is the third most common genitourinary cancer and the most common primary renal neoplasm. Estimates of the economic burden of RCC in the United States range from approximately $400 million (in year 2000 dollars) to $4.4 billion (in year 2005 dollars). Actual costs associated with RCC, particularly for elderly Medicare patients who account for 46% of U.S. patients hospitalized for RCC, are poorly understood. To estimate all-cause health care costs associated with RCC using the combined Surveillance Epidemiology and End Results (SEER)-Medicare database. The sample was limited to non-HMO patients aged 65 years or older who were diagnosed with a first primary RCC (SEER site recode 59, kidney and renal pelvis) between 1995 and 2002. Our final sample included 4,938 patients with RCC and 9,876 non-HMO noncancer comparison group cases without chronic renal disease drawn from the SEER 5% Medicare sample and matched by a propensity score calculated from age, gender, race/ethnicity, and comorbidities. Costs were defined as payments made by Medicare for all-cause medical treatments including inpatient stays, emergency room visits, outpatient procedures, office visits, home health visits, durable medical equipment, and hospice care, but excluding out-patient prescription drugs. Using the method of Bang and Tsiatis (2000), we estimated cumulative costs at 1 and 5 years by estimating average costs for each patient in each month up to 60 months following diagnosis. Total costs were weighted sums of monthly costs, where weights were the inverse probability that the patient was not censored, and inverse probabilities were estimated by Kaplan-Meier estimates of time to censoring. Using the method of Lin (2000), we performed multivariate analyses of costs by fitting each of the 60 monthly costs to linear models that controlled for demographic characteristics and comorbidities. Marginal effects of covariates on 1- and 5-year costs were obtained by summing the coefficients for months 1 through 12 and months 1 through 60, respectively. Confidence intervals were obtained by bootstrapping. Patients with RCC and matched comparison group cases had similar demographic characteristics, comorbidities, and chronic conditions. At the start of the fifth year post-diagnosis, there were 1,208 Medicare RCC cases of the original 4,938 (20.8%). Mean costs per patient per month (PPPM) in the first year were $3,673 for patients with RCC and $793 for comparison group patients. PPPM costs were higher for RCC patients with more advanced stage (i.e., regional or distant) disease. Average cumulative total costs for RCC patients were $33,605 per patient in the first year following diagnosis and $59,397 per patient in the first 5 years following diagnosis. Several patient-specific factors were associated with 1- and 5-year costs in multivariate analyses, including age, race/ethnicity, and comorbidities. Among RCC patients, treatment with surgery and radiation was associated with higher costs per patient than treatment with surgery alone at 1 year ($24,556, 95% CI = $16,673-$32,940) and 5 years ($30,540, 95% CI = $17,853-$43,648). RCC patients who received chemotherapy as part of their treatment regimen also had significantly higher costs per patient than those who received surgery alone at 1 year ($15,144, 95% CI = $ 9,979-$20,344) and 5 years ($13,440, 95% CI = $1,257-$27,572). Newly diagnosed RCC is associated with a significant economic burden, which is largely determined by several patient characteristics, disease stage, and treatment choice.