Reducing locoregional, beyond distant, recurrences, overall survival in nonmetastatic breast cancer can be improved. Although breast-conserving surgery (BCS) is the standard approach for early breast cancer, women at high risk may benefit from a more aggressive surgery that has been dramatically increased in the USA. This article evaluates the potential impact of genetics and genome-wide-association studies (GWAS) for tailoring a risk-stratification-based surgery. Data for this review were obtained by searching PubMed for articles published until 30 September 2008. Emphasis was given on data stratifying patients into high risk and low risk for local recurrence or new tumor in the affected breast (IBC) and contralateral breast cancer (CBC) according to population-based familial BRCA1/2, familial non-BRCA1/2 and sporadic breast cancer considering multiple host-related and treatment variables. Longer than 10-years follow-up results indicate that IBC/CBC as isolated first events after treatment for early breast cancer is a serious problem and may worsen overall survival. At highest risk of local failures are patients with BRCA-positive testing. However, these high-penetrance cancer genes are rare in the population. Classic clinicopathological risk factors including surgical margins, multifocality, and treatment (radiation, empirical cytotoxic chemotherapy, and newer targeted therapies including aromatase inhibitors and trastuzumab) affect IBC/CBC risk. Latest GWAS have identified novel genes with common single-nucleotide-polymorphisms (SNPs)], but these variants confer only a modest risk for breast cancer development. Future GWAS identifying further SNPs and copy-number-variants (CNVs), some of which may be involved in local failures mechanisms, will allow patient risk stratification. To prevent long-term local failures careful selection of candidate patients for BCS is required for sporadic and familial non-BRCA cancer, while bilateral mastectomy can be considered for BRCA-positive patients. Human genetic variation may play an important role in locoregional tumor control. Future prospective, large-scale, population-based studies considering multiplicative interactions between novel variants (SNPs/CNVs) and environmental factors may lead to personalized, risk stratification-based breast cancer surgery.