DEAR EDITOR, The sonic hedgehog pathway is overactive in basal cell carcinoma (BCC). 1–4 Vismodegib is the first-in-class smoothened inhibitor approved for the treatment of locally advanced or metastatic BCC. 5 Vismodegib shows major clinical benefit in patients with basal cell naevus syndrome, 6 or unresectable or metastatic BCC. 7 The most common side-effects of vismodegib are muscle cramps (71Á7%), alopecia (63Á8%) and dysgeusia (55Á1%). Here we describe the rapid occurrence of several moderate to highly differentiated squamous cell carcinomas (SCCs) in a patient treated with vismodegib. A 84-year-old white woman presented with multiple BCCs, an ulcerated BCC of the nose and multiple sharply demarcated erythematous plaques diagnosed as actinic keratosis (in situ carcinoma of the skin) on her face, lower lip and forearms (Fig. 1a). The patient had a history of excessive sun exposure with prolonged leisure time over decades of outdoor activities. Over the past decade the patient had developed numerous BCCs that were confirmed by conventional haematoxylin and eosin histology and excised. Until presentation to our department no lesions compatible with invasive SCCs of the skin had been observed. The patient was not a candidate for surgery due to the widespread ulcerated BCC on her nose and another BCC adjacent to her right epicanthus that would have required extensive mutilating surgery (Fig. 1a). Radiation therapy was contraindicated because of the high risk of chondronecrosis of the nose. She had a previous history of hypertension, diabetes mellitus, renal insufficiency at the stage of compensated retention (creatinine 1Á46 mg dL À1, normal level< 1Á09 mg dL À1) and myasthenia gravis. Dermatological examinations revealed a 4 9 5-cm ulcer on the right nasal ala with crust and haemorrhage and a 2 9 1-cm erythematous translucent plaque on the right epicanthus (Fig. 1a). Moreover, multiple crusts on an erythematous base on her face were found, compatible with in situ carcinoma (actinic keratosis). In addition, there was an apparent actinic keratosis of the right cheek (Fig. 1a).(a)(b)