p63, p73 and p53 are transcription factors members of the p53 gene family involved in development, differentiation and cell response to stress. p53 gene is mutated in 50% of human cancer. Moreover, when p53 gene is not mutated then its tumour suppressor pathway is lost through interaction with abnormally expressed cellular protein or viral protein. Therefore p53 pathway inactivation is a common denominator to cancer. However, it is still difficult to associate in the clinic p53 status to cancer prognosis and diagnosis. Recent publications may have a profound impact on our understanding of p53 tumour suppressor activity. p63, p73 and p53 genes have a dual gene structure conserved in drosophila, zebrafish and man. They encode for multiple p63, p73 or p53 proteins containing different protein domains (isoforms) due to multiple splicing, alternative promoter and alternative initiation of translation. The interplay between p53, p63 and p73 isoforms are likely to be fundamental to our understanding of tumour formation.