The aim of this study was to assess HER2 protein overexpression and the secondary gene’s amplification using CISH (Chromogenic In Situ Hybridization)-improved NGS (Next-Generation Sequencing) p53-mutated endometrial carcinomas to determine if this could be a good approach for future studies on new targeted therapies to add to the therapeutical panel of endometrial cancer. This evidence concerns the gene TP53 and endometrial cancer.