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PPM1D(protein phosphatase magnesium-dependent 1δ) maps to the 17q23.2 amplicon and is amplified in ∼8% of breast cancers. The PPM1Dgene encodes a serine threonine phosphatase, which is involved in the regulation of several tumour suppressor pathways, including the p53 pathway. Along with others, we have recently shown that PPM1Dis one of the drivers of the 17q23.2 amplicon and a promising therapeutic target. Here we investigate whether PPM1Dis overexpressed when amplified in breast cancers and the correlations between PPM1Doverexpression and amplification with clinicopathological features and survival of breast cancer patients from a cohort of 245 patients with invasive breast cancer treated with therapeutic surgery followed by adjuvant anthracycline-based chemotherapy. mRNA was extracted from representative sections of tumours containing >50% of tumour cells and subjected to TaqMan quantitative real-time PCR using primers for PPM1D and for two housekeeping genes. PPM1D overexpression was defined as the top quartile of expression levels. Chromogenic in situhybridization with in-house-generated probes for PPM1Dwas performed. Amplification was defined as >50% of cancer cells with >5 signals per nucleus/large gene clusters. PPM1Doverexpression and amplification were found in 25 and 6% of breast cancers, respectively. All cases harbouring PPM1Damplification displayed PPM1D overexpression. PPM1D overexpression was inversely correlated with expression of TOP2A, EGFR and cytokeratins 5/6 and 17. PPM1Damplification was significantly associated with HER2 overexpression, and HER2, TOP2Aand CCND1amplification. No association between PPM1Dgene amplification and PPM1D mRNA overexpression with survival was observed. In conclusion, PPM1Dis consistently overexpressed when amplified; however, PPM1D overexpression is more pervasive than gene amplification. PPM1Doverexpression and amplification are associated with tumours displaying luminal or HER2 phenotypes. Co-amplification of PPM1Dand HER2/TOP2Aand CCND1are not random events and may suggest the presence of a ‘firestorm’ genetic profile.