The p53 tumor suppressor gene acts as a great protagonist in deciding how cells undergo either cell cycle arrest or apoptosis after experiencing various stress signals, including DNA damage, hypoxia, oncogene activation, and hyperproliferation. Research on p53 is in steady expansion, as evidenced by the continual flood of papers claiming novel mutations, gain or loss of p53 functions, and gene interactions. The latest study carried out by Spurgers of Texas University and his Colleagues (J Biol Chem 2006; 281:25134-42) emphasizes the strong impact of p53 in the complicated machinery that regulates cell cycle progression. In this paper, microarray data and well-evaluated statistical procedures on PC3 and LNCaP prostate carcinoma cells, open new perspectives in p53 mechanisms and bring the simultaneous identification of novel p53-repressed cell cycle genes, hopefully providing significant improvements in the study of DNA damage response, multistep carcinogenesis, and treatment rationales and outcomes.