<h4>Background</h4>We aim to identify the prevalence and the role of the <i>MAP2K1 K57N</i> mutation in predicting resistance to anti-EGFR agents in metastatic colorectal cancer (mCRC) patients.<h4>Methods</h4>We retrospectively reviewed tumor-based next generation sequencing (NGS) results from mCRC patients screened for enrollment in the GO40872/STARTRK-2 clinical trial between July 2019 and March 2021. This evidence concerns the gene MAP2K1 and neoplasm.