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Background: Breast cancer is the greatest common cancer in women worldwide, with approximately 1.7 million new cases diagnosed each year in the world which accounts for 12% of all new cancer cases and 25% of all cancers in women. Even though the higher mortality rate of breast cancer in low and middle-income countries, the practice of early detection methods is low and the majority of the patients who appeared at an advanced stage of the disease need palliative care with little survival rates. However, evidence is scarce on the knowledge and practice of breast cancer early detection methods among women of reproductive age in Ethiopia. Therefore we aimed to assess the knowledge on risk factors and practice of early detection methods of breast cancer among female graduating students of Debre Tabor University., Methods: Institution-based cross-sectional study was conducted. A stratified random sampling technique was used. Data were collected with a self-administer questionnaire. The collected data were processed and analyzed with the computer using SPSS version 25 software. Descriptive statistics were used to describe the socio-demographic information of participants. Binary and multivariable logistic regression with an adjusted odds ratio (AOR) and 95% confidence interval (CI) was used to identify factors associated with the outcome variable. Statistical significance was stated at p < 0.05., Result: A total of 270 female students participated in the study. The median age (± SD) was 24.63 years (± 1.26). All of the students heard about breast cancer and early detection methods. About 206 (76.67%) of the participants had good knowledge of breast self-examination. Mass media, health professionals, and friends in combination were the main source of information 172 (63.77%), only 110 (40.70%) of students performed a breast-self-examination and the rest did not perform it due to forgetting fullness and lack of knowledge. About 208 (77.1%) of the respondents respond family history is a risk factor for breast cancer. Being a health science student (AOR = 2.32; 95% CI: 2.12, 3.52), family history of breast problems (AOR = 3.41; 95% CI: 3.22, 8.33), and having a good level of knowledge (AOR = 1.83; 95% CI: 1.01, 5.68) were the factors associated with the practice of breast self-examination., Conclusion: Most of the participants were unaware of the benefits, appropriate timing, and techniques of doing a breast self-examination. Health science students had better awareness & practice of breast self-examination than non-health science students. Trained health professionals must give focus on giving health information regarding risk factors of breast cancer and methods of early detection of breast cancer to the public & their clients., (© 2022. The Author(s).)