Sporadic BCC and MB, a malignant brain tumour in children, harbour high frequency of inactivating mutations in PTCH1 (Refs 99, 100, 101, 102, 103) or, to a lesser extent, activating mutations in SMO (Refs 64, 104), both leading to the constitutive activation of HH pathway. The gene discussed is PTCH1; the disease is skin basal cell carcinoma.