Abstract Background Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap. Methods/design This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor–patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor–patient consultation; as well as the length of the doctor–patient consultation. Discussion Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient’s distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases). Trial registration German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.