Context: Few studies have examined the validity of using a single item from the Edmonton Symptom Assessment Scale (ESAS) for screening for depression. Objectives: To examine the screening performance of the single-item depression question from the ESAS in chronically ill hospitalized patients. Methods: A total of 162 chronically ill inpatients aged 65 and older completed a survey after admission that included the well-validated, 15-item Geriatric Depression Scale (GDS-15) and four single-item screening questions for depression based on the ESAS question, using two different time frames ("now" and "in the past 24 hours") and two response categories (a 0-10 numeric rating scale [NRS] and a categorical scale: none, mild, moderate, and severe). Results: The GDS-15 categorized 20% (n = 33) of participants as possibly being depressed with a score ≥6. The NRS for depression "now" achieved the highest level of sensitivity at a cutoff ≥ 1 (68.8%), and an acceptable level of specificity was obtained at a cutoff of ≥5 (82.2%). For depression "in the past 24 hours," a cutoff of ≥1 achieved a sensitivity of 68.8% and a cutoff of ≥7 a specificity of 80.3%. For the categorical scale, a cutoff of "none" provided the best level of sensitivity for depression "now" (65.6%) and "in the past 24 hours" (81.3%), with an acceptable level of specificity being obtained at ≥"mild" (68.8%) and ≥"moderate" (68.8%), respectively. Conclusion: These single-item measures were not effective in screening for probable depression in chronically ill patients regardless of the time frame or the response format used, but a cutoff of ≥5 or "mild" or greater did achieve sufficient specificity to raise clinical suspicion. © 2012 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved.