The objectives of this study were to evaluate the reliability, validity, and utility of a newly developed clinical syndrome approach to assessing cancer-related fatigue. Fifty-one patients who underwent blood or marrow transplantation an average of 6.9 months previously were administered a standardized interview designed to identify the presence of a clinical syndrome of cancer-related fatigue. Patients also completed self-report measures of fatigue, depression, and health-related quality of life. Comparisons among independent raters demonstrated high rates of reliability for the presence or absence of a cancer-related fatigue syndrome and its symptoms. Twenty-one percent of patients (n = 11) were found to meet criteria for diagnosis of a cancer-related fatigue syndrome. Compared to patients not meeting the diagnostic criteria, patients meeting the criteria reported fatigue that was greater (P < or = 0.05) in its severity, frequency, pervasiveness, and interference with quality of life. Patients who met criteria also demonstrated poorer role functioning, less vitality, and more depressive symptomatology (P < or = 0.05). These findings provide preliminary evidence of the reliability and validity of the methods used to assess the proposed clinical syndrome and suggest their utility in identifying patients experiencing clinically significant cancer-related fatigue.