Analogous to retinoblastoma [11, 12] and other autosomal dominant forms of heritable cancer [13–18], BCCs in BCNS patients, arise through a two-hit mechanism in which “one hit” is an inherited, inactivating mutation in PTCH1, and the second hit is a somatically derived mutation in the remaining PTCH1 allele [7]. The gene discussed is PTCH1; the disease is cancer.