Objectives: To explore the evolution of distress amongst patients with advanced cancer at the end of life, from the time of referral to palliative care services to death. The primary outcome measure was global distress. Secondary measures were physical, psychological, social and spiritual distress. Methods: A mixed methods longitudinal study: One hundred advanced cancer patients, newly referred to the community services of a central Scotland hospice, were recruited consecutively. A 20 patient sub-sample was purposively selected for qualitative study. Assessments were monthly for 6 months maximum, each comprising the NCCN Distress Thermometer (DT), Memorial Symptom Assessment Scale (MSAS), Edinburgh Depression Scale (EDS), FACIT-Sp-12 (FACIT); qualitative data was derived from in-depth interviews. Results: Perception of receiving inadequate information and social dysfunction were independent predictors of global distress according to multivariate analysis. Increased opioid doses, out-of-hours home visits and unscheduled admissions were significantly associated with global distress. Over time, physical, psychological and spiritual distress levels initially fluctuated, prior to stabilising at a lower level, with occasional exacerbations of distress. Global Distress fluctuated constantly, yet correlated significantly (p<0.001) with MSAS, EDS and FACIT. Patients’ perspectives evolved with time, indicating reconciliation with death, despite unpredictable exacerbations of distress, reflecting transient loss of control. Conclusions: Independent predictors of distress at the end of life have been identified. Global distress was associated with an increased healthcare burden through greater service input requirements. Patient perspectives qualified the quantitative data, together indicating that from the time of referral to palliative care services, patients with advanced cancer, receiving community palliative care input, appear to become reconciled to death. However, at the end of life, transient loss of control mediated episodic, unpredictable exacerbations of distress, which were detected by the NCCN DT.