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Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case–control study conducted in Korea. We recruited 1,385 eligible patients with histologicaly confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (−786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the −786T > C or 894G > T genotype and breast cancer risk. However, the −786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56–1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59–0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women.