Background: The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area. Objective: To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables. Methods: Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients' medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS. Results: Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socio-economic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression. Limitations: Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size. Conclusion: In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.