We describe the development and validation of a rapid p53 functional assay directly performed on patient’s blood samples. This assay is based on the measurement, using RT-QMPSF and RT-MLPA, of the p53 transcriptional response in blood cells exposed to genotoxic agents. This assay, which yields a result within one week, constitutes a new tool for the interpretation of germline TP53 variants of uncertain significance. It can also unmask cryptic alterations located within TP53 non-coding regions which are not analysed by diagnostic laboratories. The article presents the analysis of 77 patients using the blood p53 functional assay (By Dr Isabelle Tournier, https://jmg.bmj.com/content/early/2020/10/13/jmedgenet-2020-107059 ).