Anemia is a multi-symptom syndrome involving both physical and emotional problems that can be evaluated for their impact on quality of life. Fatigue is the cardinal symptom of anemia, reported by three of four cancer patients using the general version of the Functional Assessment of Cancer Therapy (FACT-G) questionnaire. A subscale of the FACT-G, consisting of the FACT-Fatigue (FACT-F) and the FACT-Anemia (FACT-An), has been developed to specifically address this problem. The FACT-F is comprised of the FACT-G plus 13 questions related to fatigue, while the FACT-An is comprised of the FACT-F plus an additional set of seven miscellaneous (non-fatigue) questions relevant to anemia in cancer patients. The FACT-An subscale was initially validated in a cohort of 50 cancer patients. Tests of internal consistency and stability confirmed the reliability of the fatigue component, as well as that of the FACT-G (27 items), the FACT-F (FACT-G plus 13 fatigue items), and the FACT-An (FACT-G plus 20 anemia subscale items) measurement systems. Quality of life scores on these FACT scales significantly decline as patient performance status worsens, and the scales correlate well with other questionnaires (Profile of Mood States and Piper Fatigue Scale) purported to measure the same thing. The scores on the FACT-An subscale also clearly differentiate between patients with low and high hemoglobin levels. Low hemoglobin levels are associated with greater fatigue, poorer overall quality of life, and decreased ability to work (beyond that related directly to fatigue). Interventions that reverse fatigue and other anemia-related symptoms should have a positive effect on quality of life.