An improved understanding of the molecular characteristics of HER2-amplified CRC models and their potential mechanisms of resistance to HER2-directed therapy may influence the direction of future research on targeted therapies and inform future therapeutic decision-making.With this aim, starting from quadruple wild-type human CRC cells for KRAS, NRAS, BRAF and PI3KCA genes (LIM1215 and SW48), we have generated HER2-amplified (LIM1215-HER2 and SW48-HER2) cells. Here, KRAS is linked to colorectal carcinoma.