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The study of depression in cancer patients has been hampered by difficulty in establishing diagnostic criteria, since neurovegetative signs and symptoms may be attributable either to depression or physical illness. Confusion has also arisen in defining the boundary between “normal” grieving with illness, and “abnormal” clinical depression. We studied 62 oncology inpatients applying DSM-III diagnostic criteria, patient self-report, and interview report rating scales. Forty-two percent met criteria for nonbipolar major depression: 24% with severe and 18% with moderately severe symptoms. Fourteen percent of the sample had depressive symptoms that did not meet criteria for a major depression. Forty-four percent had no depressed affect. Medical and demographic variables were evaluated for relationship to depression; only greater degree of physical disability was clearly associated. Other negative life events and poor quality of social supports were additionally associated with depression in the less disabled patients. The use of clearly defined criteria for diagnosis of depression in cancer patients provides a basis for the study and implementation of specific therapeutic interventions.