A recent sequencing analysis of a series of 86 pairs of primary solid tumors and matched brain metastasis, including 21 cases with breast cancer primary, demonstrated that in 53% of cases, at least one clinically actionable genetic alteration was restricted to the brain metastasis, in particular alterations that may confer sensitivity to PI3K/AKT/mTOR, CDK, HER2/EGFR and MAPK pathway inhibitors [34]. The gene discussed is PIK3CA; the disease is breast carcinoma.