The phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) gene encodes for p110α—the catalytic subunit of PI3K—and is one of the most frequently mutated genes in invasive breast cancer (~26% of the cases), with most mutations clustered in either the helical domain (coded in exon 9) or in the catalytic domain (coded in exon 20), therefore named ‘hotspot’ regions [17]. The gene discussed is PIK3CA; the disease is invasive breast carcinoma.