Personalized medicine is a major goal. Novel genetic and genomic tools are needed to guide prevention and treatment of current common complex diseases including heart and cancer. Decision on surgery for localized breast cancer has now become controversy. More aggressive surgery to prevent local recurrence and contralateral breast cancer (CBC) is being increasingly selected by more patients in the USA. However, this trend may harm low-risk patients and society. Genetic testing in selecting BRCA1/2 mutation carriers for more extensive surgery is a crucial step towards individualized surgery. However, for the vast majority of patients with a family history and BRCA1/2-testing negative or the remaining women with sporadic cancer, there is no robust predictor of risk of local relapse or CBC. Genomewide association studies provide the most rational way to risk assessment-based surgery. This perspective article discusses how BRCA testing and 'classic" risk factors can be integrated into individualized surgical decisions. Furthermore, describes how rapid technological advances with cheaper high-throughput DNA sequencing techniques allow the identification of single-nucleotide-polymorphisms (SNPs) and structural genomic variation (deletions, duplications, copy number variation [CNV]). This report also discusses potential ways to overcome challenges in developing and translating microarray SNPs/CNV-chips into personalized surgical practice.