Elevated expression of nitric oxide synthase 2 has been recently shown to correlate with poor survival in estrogen receptor-negative breast cancer. In an article in Breast Cancer Research, Switzer and colleagues identify the transcription factor Ets-1 as a critical mediator of nitric oxide-dependent oncogenic gene expression in basal-like breast cancer. This pathway is driven by S-nitrosylation of wild-type Ras, which leads to mitogen-activated protein kinase-dependent phosphorylation and activation of Ets-1. These results establish a new role for S-nitrosylation in mediating an aggressive breast cancer phenotype.