Goals of work The aim of the study was to examine the role of five general personality traits in fatigue in a group of patients with breast cancer (BC) and a group with benign breast problems (BBP). Materials and methods Of the 304 participating women, 127 patients had BC and 177 BBP. A fatigue scale was completed before diagnosis and 1, 3, and 6 months after diagnosis (benign patients) or surgical treatment (BC patients). A personality questionnaire (NEO-FFI) and a depression scale (CES-D) were completed before diagnosis. Main results The BC group was less tired before diagnosis, more tired 1 month after diagnosis, and equally tired 3 and 6 months after diagnosis. In the total group, women were more tired over time when they were more neurotic, less agreeable, or more introverted. After controlling for depressive symptoms, demographics, and medical factors, baseline depressive symptoms (β=0.29, p<0.05), neuroticism (β=0.29, p<0.05), and extraversion (β=−0.25, p< 0.05) predicted fatigue 6 months later. After also including baseline fatigue, only neuroticism (β=0.22, p<0.05) and baseline fatigue (β=0.79, p<0.001) predicted fatigue.Conclusions Personality is more strongly related to fatigue than demographics, the diagnosis cancer, receiving cancer treatment, and baseline depressive symptoms and fatigue. When replicated, screening and treating women who are at risk to experience high levels of fatigue is recommended.