Fatigue is a highly prevalent and distressing symptom in cancer patients. The purpose of this study was to assess the validity of three fatigue measures [the Brief Fatigue Inventory (BFI), the Functional Assessment of Cancer Therapy Fatigue Subscale (FACT-F), and the lack of energy item from the Memorial Symptom Assessment Scale Short Form (MSAS-SF)] and compare these measures in relation to broader quality-of-life (QOL) constructs and clinical factors in veteran cancer patients. One-hundred-eighty cancer patients completed the BFI, FACT-F, FACT-G, MSAS-SF, and the Zung depression scale with concurrent Karnofsky performance status (KPS), laboratory tests, and demographic data. The Cronbach alpha coefficient was from 0.93 to 0.94 for BFI fatigue scales and 0.94 for FACT-F. There were significant correlations between BFI subscales, FACT-F, and lack of energy from MSAS-SF (p < 0.0001). All three fatigue measures showed significant correlation with MSAS-SF symptom subscales (p < 0.0001), FACT-G subscales (p < 0.0001), depression (p < 0.0001), KPS (p < 0.0001), inpatient status (P < 0.0001), insomnia (p < 0.05), hemoglobin (p < 0.05), and albumin levels (p < 0.01). Distress from lack of energy discriminated among levels from the BFI, FACT-F, and FACT-G subscales and MSAS-SF subsclea by one-way of variance analysis. Patient responses to BFI, FACT-F, and the lack of energy item yielded similar information about broader QOL constructs and clinical factors. Single questions about lack of energy, or fatigue severity, may provide a simple and acceptable way to assess fatigue.