Purpose: Cancer-related fatigue is a burdensome late effect of cancer treatment. A pilot study showed the effectiveness of cognitive-behavioral therapy (CBT) in fatigued survivors of childhood cancer (CCS). The aim of this study is to investigate whether the six cognitive-behavioral factors that are addressed during CBT differ in CCS compared with patients with chronic fatigue syndrome (CFS) and survivors of adult-onset cancer (ACS). Levels of self-esteem, optimism, and depressive symptoms, variables that are also related to fatigue, were also compared between groups. Methods: Retrospective analyses were performed on 34 CCS (ages 11-42 years), 102 patients with CFS, and 95 ACS who were referred for evaluation of severe fatigue. Fatigue severity, possible cognitive-behavioral fatigue maintaining factors, depressive symptoms, self-esteem, and optimism were assessed using questionnaires and actigraphy. Results: No significant differences were found in the factors coping with the experience of having had cancer, fear of cancer recurrence, physical activity, and in levels of self-esteem and optimism. CCS attributed their fatigue significantly more often to psychosocial causes and reported fewer problems in sleep/rest compared with patients with CFS. Compared with ACS, CCS reported significantly more social support, more problems in sleep/rest, and more depressive symptoms. Conclusions: There is substantial overlap in cognitive-behavioral factors that can maintain fatigue between CCS and CFS patients or ACS. Also differences were found regarding attribution of fatigue, the sleep/rest pattern, social support, and depressive symptoms that might have clinical implications when CBT for fatigue is provided to CCS.