No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire-9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or "watchful waiting." At each of 3 interviews over a 6-month period, patients completed the screening questionnaires and received a structured clinical interview to diagnose MDD. Internal consistency, area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value, and positive likelihood ratio were calculated. A maximum of 154 patients completed the DT, 133 completed the HAD-D, and 129 completed the PHQ-9. The HAD-D and PHQ-9 showed good internal consistency (α ≥ 0.77 at all timepoints). Median AUCs were 0.931 ± 0.074 for the HAD-D and 0.915 ± 0.055 for the PHQ-9. The optimal threshold was 7+ for the HAD-D, but 8+ had similar operating characteristics. There was no consistently optimal PHQ-9 threshold, but 10+ was optimal in the largest sample. The DT was inferior to the multi-item instruments. Clinicians can screen for depression in well-functioning glioma patients using the HAD-D at the existing recommended lower threshold of 8+, or the PHQ-9 at a threshold of 10+. Due to a modest positive predictive value of either instrument, patients scoring above these thresholds need a clinical assessment to diagnose or exclude depression.