Somatic mutations in PIK3CA have been found in 10–30% of colorectal cancers. KRAS, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies in metastatic colorectal cancer. According to some reports, co-occurrence of both exon 9 and exon 20 PIK3CA mutations, when present, may be associated with a poor prognosis. Recent 'molecular pathological epidemiology’ (MPE) research has shown that aspirin use may be associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation may be a molecular biomarker that predicts response to aspirin therapy. PIK3CA may also be a target of directed therapy in some clinical settings.