The aims of this study were to assess in two different settings and at two different points of time the quality of life of patients with cancer who are terminally ill, to get an insight into the changes that occur in the course of time, and to evaluate the differences between the groups. A stratified random sample of 121 patients was extracted from a total of 250 cancer patients who were being treated in the hospital or home care services. All patients have end-stage cancer and approached the unit or the specialized home care services for pain relief and management of other cancer-related symptoms. A longitudinal observational study was designed to assess the effect of palliative care during the first week of admittance to a hospital and to home care. In the hospital patients group, patients showed a statistically significant and clinically relevant decrease (improvement) in nausea/vomiting, pain, and dyspnea (effect size, >0.20). In the home care group, we did not find any statistically significant changes in sleep disturbance, financial impact, and control parameter Karnofsky index. However, statistically significant and clinically relevant improvements were detected in the domains cognitive function, physical function, new role function, emotional function, social function, fatigue, nausea/vomiting, pain, dyspnea, appetite loss, constipation, diarrhea, and new global health. The Europian Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) can be used as a brief, simple instrument that is easy to integrate into routine practice and useful for a clinical audit of palliative care in different settings as an outcome measurement and for assessing the quality of life of advanced-stage cancer patients.