Depression at the end of life is a common mental health issue with serious implications for quality of life and decision making. This study investigated the reliability and validity of one of the most frequently used measures of depression, the Hamilton Depression Rating Scale (HAM-D) in 422 patients with terminal cancer admitted to a palliative care hospital. The HAM-D demonstrated high reliability and concurrent validity with depression diagnosis, based on Structured Clinical Interview for DSM-IV Axis I Disorders, non-patient research version (SCID-I/NP Depression Module). Receiver Operating Characteristic (ROC) analyses generated an area under the curve of .91, indicating high sensitivity and specificity. The HAM-D strongly correlated with several measures of distress (e.g., hopelessness, desire for hastened death, and suicidal ideation). Factor analysis generated 4 factors (anxiety, depressed mood, insomnia, and somatic symptoms), accounting for 42% of the variance. Implications for assessing depression in this population are discussed. (Contains 5 tables, 2 figures, and 2 notes.)