Neuropsychiatric problems, and how they interact to impact on quality of life (QOL) in brain tumor patients, are generally poorly understood. The objectives of this study were: (1) to document the prevalence of depression, fatigue, emotional distress, and existential issues in a sample of brain tumor patients (2) to examine the interconnectedness of these problems, and (3) to explore their relationship with disease-related variables and QOL. This is a cross-sectional, questionnaire-based survey of 73 patients with primary brain tumors who presented to a neurological clinic at a tertiary cancer centre for ongoing care. Data for 60 participants (29 women, 31 men) who completed validated questionnaires were retained for analysis. Results showed that there was a high burden of depressive symptoms as measured by the Beck Depression Inventory-II (mean score 11.1, SD 7.4), with 38% of the sample scoring in the clinically depressed range. Overall QOL scores for this sample were similar to a reference sample of brain tumor patients. The scores on the existential subscale of the McGill Quality of Life questionnaire were comparable to those of a reference sample of cancer patients receiving ongoing care (mean score 7.2; SD 1.7). Fifty per cent of the sample could be classified as struggling with existential issues. Although scores reflecting depression, fatigue, emotional distress, and existential problems were interrelated, the presence of depressive symptoms was the single most important independent predictor of QOL in this cohort of brain fumor patients. Implications for treatment are discussed.