It is unclear what effect the EGFR P753S varaints has on the EGFR protein. However the location of the variant in the splice site acceptor of Exon 19 may activate the kinase domain. The identification of the EGFR P735S mutation in the context of a dramatic response to cetuximab in a patient with cutaneous squamous cell carcinoma, indicates a new potential pairing of EGFR mutation and targeted therapy for patients with cSCC.