Somatic mutations are the cornerstone of cancer (Hanahan et al. 2000). The development of cancer involves the contributions of many heritable genetic events as well as of a large number of epigenetic changes, but what makes the turning point between untransformed and transformed cell irreversible is the acquisition of targeted, somatic mutations, conferring to cells a selective advantage for clonal proliferation. These mutations can occur in many different genes, but only a handful of them are frequently mutated in a wide variety of human cancers. They include genes of the RAS family (mainly KRAS), BRAF1, APC,α–Catenin, p16/INK4a, PTEN and TP53. After over 20 years of research on mutation detection in cancers, TP53 remains the world champion of somatic mutations, with over 70 % of all the mutations described so far in human cancers (Hainaut et al. 2000).