The emergence of RAS-mutant clones in the plasma of patients with initially wilde-type RAS tumors has been also widely described, inducing a close monitoring of the onset of secondary resistance to anti-EGFR therapy and generating new hypotheses for blood- guided therapeutic strategies16,27 We identified 12% of cases in which patients tested RAS WT by tissue biopsy of the primary tumor were found to be mutated in metastatic disease as assessed by exosome-based liquid biopsy. Here, EGFR is linked to metastatic neoplasm.