OBJECTIVES: Determine the relationship between health care expenditures and depression in individuals with cancer compared to those with cancer and depression, after controlling for demographic, socio-economic, access to care and other health status variables. METHODS: Cross-sectional data on 4766 adults from multiple years (2006, 2007, 2008, and 2009) of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS) were used.  Cancer and depression was identified from Medical conditions file. Dependent variables consisted of total, inpatient, outpatient, emergency room, prescription drugs and other expenditures. OLS on logged dollars and generalized linear models with log-link were performed.  All analyses accounted for the complex survey design of the MEPS. RESULTS: Overall, 14% of individuals with cancer reported having depression. Among individuals with cancer and depression the average health care expenditures were $18,401compared to $12,091 among those without depression. After adjusting for demographic, socio-economic, access to care and other health status variables, those with depression had about 32% greater total expenditures compared to those without depression. Expenditures for every type were higher among individuals with depression compared to those without depression.  Individuals with cancer and depression were more significantly more likely to use emergency rooms (AOR = 1.46) and prescription drugs (AOR = 3.56) compared to their counterparts without depression.  CONCLUSIONS:   Among adults with cancer, those with depression had higher health care utilization and expenditures compared to those without depression.  Policy efforts to reduce excess health care expenditures associated with depression may include screening for depressive symptoms and preventing major depression, timely depression treatment once depression is detected.