OBJECTIVES: Research indicates 18% to 96% of cancer patients experience fatigue due to cancer or its treatment. Only one claim for "cancer-related fatigue" (CF) has been granted by the US Regulatory Authorities. To date, the definition or diagnosis of CF remains a subject for debate within the clinical community. Although several self-completed CF-specific instruments are available, the lack of an accepted conceptual framework articulating those concepts important to patients has hampered research in this field. Developing a preliminary conceptual framework able to underpin patients' experience of CF is central to gather meaningful data. Qualitative articles with verbatim patient quotes were reviewed and synthesized to begin a large effort to develop such a framework. METHODS: A systematic search identified 95 articles published between 1996 and 2007 containing patient quotes. Search terms included fatigue, tiredness, lassitude, weakness, or asthenia. Two researchers independently reviewed articles; 645 quotes were extracted and systematically analyzed to identify concepts and language used to describe patients' CF experiences. RESULTS: CF is more intense than pre-diagnosis or treatment tiredness. Terms such as “overwhelming,” “unusual,” and “all-encompassing” were used to describe CF. Quotes referring to “tiredness” were often associated with adverbs (very, extremely) or patients' idiomatic phrases intensifying “tiredness” (e.g., “dead-tired”, “sick-tired”) to distinguish tiredness due to CF. Metaphors depicted the severity and debility associated with CF. CONCLUSIONS: Findings suggest that extant CF assessments fail to capture the unique experience of CF as described by patients. Publication bias and lack of primary data from which quotes were drawn are study limitations. Rigorous qualitative research with patients with different types and stages of cancer is needed to concisely and comprehensively describe the experience of CF and its impact.