Employing targeted deep sequencing of 39 squamo-proliferative lesions from seven patients (including cSCC and actinic keratosis (Supplementary Table 1) treated with vemurafenib (using a percentage variance criterion of >10%), we identified frequent coding mutations in both TGFBR1 (8/39, 21% of samples) and TGFBR2 (5/39, 13% of samples), revealing mutation of TGFβ receptors in 28% of lesions (Fig. 1a and Supplementary Data 1). Here, TGFBR2 is linked to skin squamous cell carcinoma.