Breast disease often presents as palpable masses (lumps), inflammatory lesions, nipple secretion, or mammography abnormalities; and this can be easily treated when discovered early. Breast Self-Examination (BSE) is the quickest and cheapest means of early breast cancer detection. The objective of this study was to determine the knowledge and practice of breast self-examination among female undergraduates in Owerri, south eastern Nigeria. A multi-stage sampling design was used to select participants. Interview using structured questionnaire was conducted on randomly selected respondents in six faculties from each tertiary institution. Questionnaire was prepared in English and was self-administered. Permission to conduct the survey was requested and obtained from the university ethical review board. Informed verbal and written consent was obtained from participants. Confidentiality of information was maintained throughout the study. Knowledge and practice of BSE was examined among 720 randomly selected female undergraduates aged 16 to 28 years. It was found that 98.9 percent have heard of BSE but only 32.5 percent of them performed this examination accurately and monthly as required. There is a statistically significant relationship between knowledge of risk factors for breast cancer and practice of BSE (χ2 = 31.17, P χ2 = 86.75, P χ2 = 75.94, P < 0.001). These female undergraduates had a poor knowledge of the right procedure and practice of BSE; therefore there is need for awareness creation on the risks of breast cancer and benefits of early detection among female undergraduates through breast self-examination.