Here, we characterized the MMR status in a large series of breast cancers to define 1) the frequency and clinicopathologic features of dMMR breast cancers, 2) the concordance and interchangeability of IHC and MSI analysis for these patients, 3) the impact of intra-tumor heterogeneity, and 4) the prognostic and predictive role of MMR defects in breast cancers. The gene discussed is MRC1; the disease is breast cancer.