Molecular subtypes, including the human epidermal growth factor receptor 2-enriched subtype (HER2+), drive patient outcomes in human breast cancer but the biological basis underlying subtype-specific disease is not completely understood (1-4). We mined published microarray data (5, 6) to discover in an unbiased fashion the most distinguishing genetic and transcriptional features of tumors of each breast cancer molecular subtype. We identified a single nucleotide polymorphism, rs3169914,

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... within KRT20, as among the most significant genetic differences in the tumors of patients with HER2+ breast cancer. In a separate cohort of patients with HER2+ subtype breast cancer, we observed transcriptome-wide differential expression of a KRT20 transcript. Analysis of patient survival data revealed that KRT20 primary tumor expression was correlated with distant metastasis-free survival in patients with normal-like breast cancer. Sequence variation in the KRT20 gene may be important in understanding differences in genetic background that favor development of HER2+ subtype human breast cancer.