Pathogenic BRCA1 and BRCA2 (BRCA) variation is the genetic predisposition for high cancer risk affecting mostly breast and ovarian. BRCA variation information is widely used in clinical diagnosis, treatment, and prevention of BRCA-related cancer. The positive selection imposed on human BRCA leads to highly ethnic-specific BRCA variation to adapt different living environment on earth. Most of the human BRCA variants identified so far were from the European descendant populations and used as the standard reference for global human populations, whereas BRCA variation in other ethnic populations remains poorly characterized. This review addresses the origin of ethnic-specific BRCA variation, the importance of ethnic-specific BRCA variation in clinical application, the limitation of current BRCA variation data, and potential solutions to fill the gap.