Breast cancer patients undergo extended treatments that affect their psychological state and quality of life. There is a lack of studies examining the effects of holistic stress management interventions (that combine stress perception, cognitive and lifestyle interventions) on mental health and biological indices (e.g. cortisol concentrations) of breast cancer patients.This pilot randomized controlled trial provided the first assessment of the effects of a novel, cognitive-based intervention, the Pythagorean Self-Awareness Intervention (PSAI), on psychological symptoms, quality of life, sleep quality and lifestyle as well as on stress-related biological measures of breast cancer patients undergoing adjuvant therapy. Standardized questionnaires were administered at baseline and 8-weeksafter the intervention to evaluate quality of life, stress, depression, and anxiety (primary outcomes). Sleep quality, lifestyle and hair cortisol concentrations were also assessed (secondary outcomes).Forty-five breast cancer patients undergoing adjuvant therapy were randomly assigned to the PSAI group (n = 25) or the control group (n = 20).Women in the PSAI group reported significant improvements post-intervention in total Quality of Life, specific aspects of Quality of Life [Physical well-being, Social well-being, Emotional well-being, Functional well-being, Breast cancer concerns] as well as Perceived stress, depression, anxiety and stress. Improvements in secondary outcomes included increase in sleep quality, empowerment for healthy lifestyle and reduction of hair cortisol concentrations.The PSAI was beneficial as complementary therapy in the women studied. Larger randomized controlled trials with longer follow-up are needed to ascertain these findings.