Objectives: To investigate the screening performance for frailty of the Vulnerable Elders Survey-13 (VES-13) and the 2-step approach consisting of the VES-13 plus the anhedonia (loss of interest or pleasure) item from Patient Health Questionnaire-9 (PHQ-9) among older patients with newly diagnosed cancer. Methods: This study involved 106 consecutive inpatients aged 65 years or older, newly diagnosed with malignant lymphoma or multiple myeloma, just before chemotherapy initiation. The participants were administered the VES-13, and also underwent a comprehensive geriatric assessment (CGA), including for depression and 6 other geriatric conditions, using validated measures, just before initiation of chemotherapy. We defined frailty as the presence of 2 or more geriatric conditions as determined by the CGA. Receiver operating characteristic analysis was performed. The 2-step screening approach was examined by post hoc analysis. Results: The average age of the subjects was 74 years. Among the 106 subjects, 50% met the criteria for frailty. Using a cutoff score of 2 to 3 on the VES-13, a sensitivity and negative predictive value (NPV) of 72% of the screening tool was obtained for the condition of frailty. When the second step of the screening, consisting of the VES-13 plus anhedonia, was applied to the VES-13–negative patients, the sensitivity and NPV improved to 90% and 88%, respectively. Conclusions: The 2-step approach exhibited better screening performance for frailty among patients with cancer than existing methods. Large prospective studies are required in the future to confirm this ability of the 2-step approach.