The overall driver mutations in RDEB-associated cSCC are the same as those in spontaneous ultraviolet light- induced cSCC and head and neck SCC and include genes such as HRAS, NOTCH1, TP53, and CDKN2A; however, mutations in these genes occur much earlier in life in patients with EB (4–6). Here, NOTCH1 is linked to skin squamous cell carcinoma.