Here, we analyzed the MMR and PTEN status in a large series of breast cancers to define (i) the frequency, clinicopathologic features, and prognosis of PTEN-altered tumors; (ii) the impact of intra-tumor heterogeneity in PTEN testing; and (iii) the role of PTEN in MMR status prediction. The gene discussed is PTEN; the disease is neoplasm.