Purpose A stepped care (SC) program in which an effective yet least resource-intensive treatment is delivered to patients first and followed, when necessary, by more resource-intensive treatments was found to be effective in improving distress levels of patients with head and neck cancer or lung cancer. Information on the value of this program for its cost is now called for. Therefore, this study aimed to assess the cost-utility of the SC program compared with care-as-usual (CAU) in patients with head and neck cancer or lung cancer who have psychological distress. Patients and Methods In total, 156 patients were randomly assigned to SC or CAU. Intervention costs, direct medical costs, direct nonmedical costs, productivity losses, and health-related quality-of-life data during the intervention or control period and 12 months of follow-up were calculated by using Trimbos and Institute of Medical Technology Assessment Cost Questionnaire for Psychiatry, Productivity and Disease Questionnaire, and EuroQol-5 Dimension measures and data from the hospital information system. The SC program's value for the cost was investigated by comparing mean cumulative costs and quality-adjusted life years (QALYs). Results After imputation of missing data, mean cumulative costs were -€3,950 (95% CI, -€8,158 to -€190) lower, and mean number of QALYs was 0.116 (95% CI, 0.005 to 0.227) higher in the intervention group compared with the control group. The intervention group had a probability of 96% that cumulative QALYs were higher and cumulative costs were lower than in the control group. Four additional analyses were conducted to assess the robustness of this finding, and they found that the intervention group had a probability of 84% to 98% that cumulative QALYs were higher and a probability of 91% to 99% that costs were lower than in the control group. Conclusion SC is highly likely to be cost-effective; the number of QALYs was higher and cumulative costs were lower for SC compared with CAU.