Background. In the Netherlands, many (45%) cancer patients die at home, in the care of GPs. About 1 out of 10 end-of-life cancer deaths is hastened by GPs through euthanasia or physician-assisted suicide. However, the relationship between depression and requests for euthanasia has never been prospectively studied directly in primary care. Objective. This study aimed to assess the prevalence of depression in end-of-life cancer patients requesting euthanasia in primary care, as well as to assess the relationship between depression and requesting euthanasia. Methods. Primary care patients with incurable cancer and an estimated life expectancy of half a year or shorter were interviewed every 2 months, using standardized psychometric instruments. Also, non-recruited eligible patients were monitored. Results. Out of 258 eligible patients, 76 patients were recruited, of whom 64 patients were followed up until death. Of these, 27% ( n = 17) explicitly requested euthanasia. One patient suffered from major depression. According to the depression subscale of the Hospital Anxiety and Depression Scale, 47% of the patients who explicitly requested euthanasia versus 28% of those without an euthanasia request suffered from a depressed mood at inclusion; the difference was not significant ( P = 0.2). Corresponding figures for the last interview before death were 40% and 41% ( P = 0.6). Conclusions. Major depression was not a major factor in explicit requests for euthanasia in end-of-life cancer patients in primary care. Further depressed mood was not associated with explicitly requesting euthanasia in this patient group, although statistical underpower cannot be ruled out in this small sample.