Fatigue, pain, distress, and anorexia are four commonly encountered symptoms in cancer. To evaluate the usefulness of a single-item screening for these symptoms, 597 ambulatory outpatients with solid tumors were administered a self-report screening instrument within the first 12 weeks of chemotherapy. Patients rated the severity of each symptom on a 0-10 scale, at its worst over the past three days, with higher ratings associated with higher symptom levels. From this sample, 148 patients also completed a more comprehensive assessment of these symptoms. Two criteria were used to determine optimal cut-off scores on the screening items: 1) the sensitivity and specificity of each screening item to predict clinical cases using receiver-operating characteristics analysis and 2) the proportion of patients at each screening score who reported that some relief of the target symptom would significantly improve their life. Optimal cut-off scores ranged from 4 to 6 depending on the target symptom (area under the curve range=0.68-0.88). Use of single-item screening instruments for fatigue, pain, distress, and anorexia may assist routine clinical assessment in ambulatory oncology practice. In turn, such assessments may improve identification of those at risk of morbidity and decreased quality of life due to excess symptom burden.