Breast cancer (BC) is the most prevalent form of cancer in the Kingdom of SaudiArabia, accounting for 11% of all female cancers. It is considered to be a progressive disease with a poor prognosis if detected late. The low level of knowledge and practice of breast self-examination is an important method of prevention. The study was aimed at assessing the knowledge of breast cancer and practice of Breast Self-Examination (BSE) among female secondary school students in Riyadh city. Material & Methods : A cross-sectional descriptive correlation design was used in this study. A representative probability sample was recruited (Sample Size = 917 Students). A self-administered questionnaire was prepared by the researcher. It consists of four parts. Data was analyzed using the SPSS software package (version 16) for data entry and analysis. Results: The results of the study indicated that none of the secondary school students had an excellent knowledge regarding breast cancer; 98.8% of the participants had a fair level of knowledge about breast cancer. The mass media was the most common source of information about breast cancer. The majority of participants did not perform breast self-examination 80.8%; only 3.4% perform (BSE) on monthly basis. Therewas a statistically significant relation between level of breast cancer knowledge and secondaryschool type, nationality, family history of breast cancer and secondary school levels but there was no significant relation between knowledgeof breast cancer and age groups, marital status and family income level. Logistic regression analysis revealed that a negative family history of breast cancer was a significant predictor for lower scores on the level of knowledge of breast cancer. However, age group, family history of breast cancer were significant predictors of performance of breast self-examination. Conclusions : This study revealed that most of the female secondary school students in Riyadh, Saudi Arabia had very low knowledge about breast cancer. We recommended developing a health educational program about breast cancer for students, teachers and the community, to raise awareness.