BACKGROUND: Cancer-related fatigue can be measured as both a unidimensional and a multidimensional construct. Unidimensional fatigue and its symptom correlates have undergone some previous investigation; however, minimal research has considered the differential effect of correlates on individual dimensions of fatigue. The objective of the current study was to investigate cancer-related fatigue in a radiotherapy sample using a multidimensional conceptualization to determine whether correlates of fatigue are consistent across all dimensions or whether each fatigue dimension has its own unique pattern of correlates. METHODS: The study used a prospective cohort design with data collected from radiotherapy patients at 3 time points; before, after, and 6 weeks after radiotherapy treatment. RESULTS: A total of 210 participants were enrolled in the study. Results indicated the following relations. Increased general fatigue was found to be associated with lower performance status, being in a de facto relationship, depression, having treatment to the brain, and reduced vigorous physical activity. Increased physical fatigue was associated with lower performance status, depression, reduced physical activity, reduced productive hours, and nausea. Higher levels of reduced activity were associated with depression, decreased participation in activities of daily living, decreased number of productive hours, and lower performance status. Higher levels of reduced motivation were associated with radiotherapy to the brain, reduced moderate physical activity, and depression. Increased mental fatigue was associated with diagnosis of a brain tumor, anxiety, depression, and sleep problems. CONCLUSIONS: The results of the current study support the recognition of multiple dimensions of fatigue, because each dimension examined had various correlates. These findings further develop our understanding of fatigue and may help clinicians provide more targeted information to people with cancer-related fatigue. Furthermore, these results can guide the development of group or individually tailored interventions that ultimately may reduce the impact of this distressing symptom on people with cancer.