Based on the presented data and supported by structural analysis and comparison with the well‐studied p53 cancer mutations we propose the novel classification of p63 ELA and SHFM4 mutations based on four different mechanisms of impairing DNA binding: mutations in the direct DNA contact interface, in the zinc binding region, in the H2 region or in the dimer interface (Table 1; Fig. 7). This evidence concerns the gene TP63 and cancer.