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Objective: Depression in patients with cancer has been associated with increased annual health care use and costs relative to nondepressed patients. Little is known of the potential cost savings associated with receipt of mental health treatment. This study evaluated the association between number of mental health visits and annual health care costs in patients with cancer and comorbid major depression. Method: Using a retrospective cohort study design, this study included 182 individuals with an ICD-9 chart diagnosis of cancer in 2014 and with comorbid major depressive disorder. The outcome of interest was annual health care charges 1 year from cancer diagnosis. Number of mental health visits was extracted from patients’ electronic medical records for the year following cancer diagnosis. A generalized linear model with a log link function and gamma distribution was used to evaluate the association between number of mental health visits and annual health care charges, covarying for age, sex, race/ethnicity, cancer site, metastatic disease, insurance status, and severity of comorbid medical conditions. Results: A significant association was found between number of mental health visits and annual health care charges (exp(B) = 0.973, 95% CI [0.949, 0.999]; p = .043). Estimated annual health care costs were $99,073 for those receiving no mental health visits and $71,245 for those receiving the sample-based mean of 12 mental health visits, inclusive of mental health visits. Conclusions: Greater dose of mental health visits was associated with lower annual health care costs. Improved screening and adequate treatment of depression has potential to reduce total health care costs among patients with cancer. Because this was a small study, few patients with exceptionally high costs could augment the results. Therefore, replication of these findings, particularly using a clinical trial design, is needed to confirm these effects.