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Fatigue is a major concern for cancer patients of all ages. The lack of an appropriate assessment tool has impeded our understanding of its prevalence and significance, specifically in the pediatric cancer population. This paper documents the reliability and validity of the pediatric Functional Assessment of Chronic Illness Therapy-Fatigue (pedsFACIT-F) in a comprehensive manner. The 11-item PedsFACIT-F was developed via literature review, feedback from patient/parent/clinician, and a face-to-face consensus meeting. Its reliability and validity were examined on the basis of data from 159 pediatric patients with cancer via classical test theory and Rasch analysis. Results showed that the pedsFACIT-F demonstrated good internal consistency (Cronbach α), acceptable item-total correlations, and met the unidimensionality assumption set by confirmatory factor analysis. All items had acceptable fit statistics in the Rasch analysis and demonstrated stable measurement properties by age, sex, and cancer type. Scores on the pedsFACIT-F significantly discriminated between patients with and without anemia and among patients with different functional status; clinically relevant minimally important differences were estimated accordingly. The pedsFACIT-F was significantly correlated to the PedsQL Multidimensional Fatigue Scale. In conclusion, the pedsFACIT-F demonstrates satisfactory reliability and validity and can be a useful tool in clinical trials and other research.