Somatic missense mutations in the PIK3CA gene have been reported in 15% of cancers, including 10-30% of colon cancers, 25% of breast cancers, 23% of endometrial cancers, 13% of cervical cancers, 6% of liver cancers, diffuse 1-3% of large B-cell lymphomas, and 4% of lung cancers. In most tissue types, mutations predominantly cluster within the three hotspots: E542K (17%), E545K (28%), and H1047R (21%). Based on data from the Catalogue of Somatic Mutation in Cancer (COSMIC) database, point mutations in these three codons account for more than 80% of PIK3CA mutations. These somatic missense mutations cause increased kinase activity of p110 catalytic subunit of PI3K (PIK3CA), contributing to cellular transformation. PIK3CA is a 34 kb gene located on chromosome 3q26.3 that consists of 20 exons coding for 1068 amino acids yielding a 124 kDa size protein. Mutations in PIK3CA may predict treatment sensitivity to mTOR inhibitors.