Psychological distress is a common consequence of breast cancer diagnosis and treatment and could further exacerbate therapy side effects. Interventions increasing treatment tolerance are crucial to improve both patients' quality of life and adherence to therapies. Virtual reality (VR) has emerged as an effective distraction tool for different medical procedures. Here, we assessed the efficacy of immersive and interactive VR in alleviating chemotherapy‐related psychological distress in a cohort of Italian breast cancer patients, also comparing its effects with those of music therapy (MT). Thirty patients were included in the VR group, 30 in the MT group, and 34 in the control group, consisting of patients receiving standard care during chemotherapy. Our data suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, VR seems more effective than MT in relieving anxiety, depression, and fatigue. The efficacy of virtual reality (VR) has been tested versus music therapy (MT) and a control group. The results of our study suggest that both VR and MT are useful interventions for alleviating anxiety and for improving mood states in breast cancer patients during chemotherapy. Moreover, the VR intervention seems more effective than MT in relieving anxiety, depression, and fatigue. Thus, despite its limitations, this study supports the continuous research on VR as a distraction intervention able to meet the global clinical need for effective nonpharmacologic adjuncts.