The development and elaboration of a conceptualization of existential distress in patients with advanced disease is crucial in order to optimize our clinical response within palliative medicine. Demoralization is one expression of existential distress. Its empirical study will be greatly enhanced by a self-report measure that captures its dimensions and intensity. We report here on the development and testing of the Demoralization Scale in 100 patients with cancer. Factor analysis identified five relatively distinct dimensions: loss of meaning, dysphoria, disheartenment, helplessness, and sense of failure. These factors show high internal reliability, and convergent validity with the McGill Quality of Life Scale, Patient Health Questionnaire, Beck Depression Inventory, Beck Hopelessness Scale, Hunter Opinions and Personal Expectations Scale, and the Schedule of Attitudes toward Hastened Death. Its divergent validity is demonstrated through the differentiation of a subgroup of patients with high demoralization who do not meet DSM-IV categorization for a diagnosis of major depression. Confirmatory validation is needed for the scale to be used as a measure of change in interventions designed to treat demoralization.