OBJECTIVES: To evaluate healthcare expenditures associated with treatment of seven TOI and define a burden of TOI to the healthcare. METHODS: Retrospective case-control study was conducted using MarketScanTM claims databases of over 3 million US employees, spouses, dependents, and early retirees. Cases were newly diagnosed with TOI in 1999-2000 (index date). Cases had no cancer diagnosis for 12 months prior to index date and had confirming diagnosis of TOI within 3 months of the index date. Control groups were members without cancer diagnosis and matched 3:1 with each case group (97.5% match) on gender, age, health coverage, region, and follow-up period. Monthly healthcare expenditures were estimated, adjusting for age, gender, Charlson Comorbidity Index, region, follow-up period, and hospital mortality using ordinary least squares with logarithmic transformation. Due to left-skewed distribution, regression-adjusted expenditures of controls were estimated using two-part models. Re-transformed expenditures (using smearing estimator) were compared with a t-test. RESULTS: The study consisted of 12,709 cases and 38,127 controls. Cases included 43% prostate, 22% colorectal, 16% lung, 5% brain, 3% ovarian and 3% pancreatic cancer, and 8% Non-Hodgkin's lymphoma patients. Mean follow-up period was 11 months. Mean monthly healthcare expenditures for cases were $3905 (SD=$2647) vs. $329 (SD=$446) for controls (p<0.0001). The highest expenditures were associated with pancreatic ($7613 vs. controls $334), ovarian ($6373 vs. controls $281), brain ($6364 vs. controls $277), and lung ($6520 vs. controls $339) cancer. Except in prostate cancer, inpatient services drove the expenditures in all TOI. CONCLUSIONS: Mean monthly healthcare expenditures associated with TOI were almost 12 times higher compared to controls. Pancreatic, ovarian and brain cancer patients had 20 times higher expenditures than control groups. The burden of the seven tumors to the healthcare system is substantial and suggests a need for increased prevention or new therapies to reduce resource use and healthcare expenditures.