The growing interest in the psychological distress in patients with cancer has been the major reason for the conduction of this study. The aims were to assess the relationship of hopelessness, anxiety, distress, and preparatory grief, as well as their predictive power to hopelessness. Ninety-four patients with advanced cancer completed the study at a palliative care unit in Athens, Greece. Beck Hopelessness Scale, the Greek version of the Hospital Anxiety and Depression (HAD) scale, and the Preparatory Grief in Advanced Cancer Patients scale were administered. Information concerning patients' treatment was acquired from the medical records, whereas physicians recorded their clinical condition. Hopelessness correlated significantly with preparatory grief (r = .630, P < .0005), anxiety (r = .539, P < .0005), depression (r = .642, P < .0005), HAD-Total (r = .686, P < .0005), and age (r = -.212, P = .040). Multiple regression analyses showed that preparatory grief (P < .0005), depression (P < .0005), and age (P = .003) were predictors of hopelessness, explaining 58.8% of total variance. In this patient sample, depression, preparatory grief, and patients' age were predictors of hopelessness.