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The purpose of this study was to investigate the relationship between optimism and emotional well\u2010being (EWB) and the individual and combined mediation of this relationship by perceived social support (SS), problem focused coping (PFC), and self\u2010transcendence in women with breast cancer during radiation therapy.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>: Ninety\u2010three women receiving radiation treatment for breast cancer completed questionnaires that measured EWB, optimism, SS, PFC, and self\u2010transcendence.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>: Correlational and multiple regression analysis revealed that optimism was positively related to EWB. Of the three mediators, self\u2010transcendence alone was found to partially mediate the relationship between optimism and EWB. The relationship between optimism and PFC was not significant. Optimism was related to SS, but its indirect effect on EWB through SS did not reach significance.<\/jats:p><jats:p><jats:italic>Conclusions and implications<\/jats:italic>: During breast cancer treatment, the positive effects of optimism on EWB are partially mediated by a woman's level of self\u2010transcendence. Brief screening of women's optimism may help identify women at risk for psychological distress. Early detection and interventions to promote psychological adjustment throughout the cancer trajectory (e.g. enhancing self\u2010transcendence) should receive attention in future research. 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