BACKGROUND: Fatigue is the most common unrelieved symptom experienced by people with cancer. The purpose of this study was to examine whether cancer-related fatigue (CRF) can be summarized using a single score, that is, whether CRF is sufficiently unidimensional for measurement approaches that require or assume unidimensionality. We evaluated this question using factor analysis techniques including the theory-driven bi-factor model. METHODS: Five hundred and fifty five cancer patients from the Chicago metropolitan area completed a 72-item fatigue item bank, covering a range of fatigue-related concerns including intensity, frequency and interference with physical, mental, and social activities. Dimensionality was assessed using exploratory and confirmatory factor analysis (CFA) techniques. RESULTS: Exploratory factor analysis (EFA) techniques identified from 1 to 17 factors. The bi-factor model suggested that CRF was sufficiently unidimensional. CONCLUSIONS: CRF can be considered sufficiently unidimensional for applications that require unidimensionality. One such application, item response theory (IRT), will facilitate the development of short-form and computer-adaptive testing. This may further enable practical and accurate clinical assessment of CRF.