Background: Breast cancer (BC) remains a major global health concern with significant impact on women.  Given the limited research among Jordanian adolescents, this study examines the knowledge and attitude of Breast Self-Examination (BSE) among secondary school female students. Methods: A cross-sectional design using convenience sampling was employed to recruit 330 female secondary school students. Results: The findings revealed that while most students (68.8%) had some awareness of BC, overall knowledge was limited, with a mean score of 4.7 out of 21. Only a small percentage accurately identified key BC risk factors, symptoms, and BSE practices. Attitude scores indicated a moderate positive attitude, with a mean score of 25.18 out of 60. Regression analysis showed that significant predictors of knowledge included the source of information, presence of a family history of BC, and the closeness of the familial relationship to the affected individual. Attitudes were significantly associated with the father's education level and family relationship to the affected family member, but not with overall knowledge scores. Conclusions: Findings highlight critical gaps in BC and BSE knowledge among Jordanian adolescents, with family-related factors serving as key predictors of both knowledge and attitudes. Implications for Nursing: School and community health nurses are well positioned to implement culturally sensitive awareness programs, engage families in reinforcing positive attitudes, and advocate for integrating BC education into school curricula. Enhancing nursing-led educational interventions may improve students’ knowledge, encourage early detection practices, and contribute to better long-term community health outcomes.