UV light exposure from bright sunlight or tanning beds leads to p53 mutations that contribute to skin cancer development in most of the 1 million individuals diagnosed with nonmelanoma skin cancer in the US each year. In a report in this issue of the JCI, Tang et al. (17) demonstrate that CP-31398 (13) can prevent UVB-induced tumor development as well as serve as an effective treatment for tumors that develop in an immunocompetent mouse model. CP-31398 appears to promote apoptosis by restoring wild-type p53 activity to mutated p53, leading to increased proapoptotic Bax expression, reduced antiapoptotic Bcl2 expression, and cytochrome c release from mitochondria. The inset shows the spectrum of p53 mutations observed in human squamous cell cancer of the skin that is associated with UVB exposure (UMD p53 mutation database: http://p53.free.fr/Database/p53_cancer/p53_skin.html). Mutations occur at particular hot spots with greater frequency, leading to loss of p53 tumor suppressor function. BCC, basal cell carcinoma.