Although a number of preclinical and clinical studies conducted in BCC and MB patients have documented a significant initial efficacy of the treatment [93,94,95,96], use of vismodegib has been invariably associated with the appearance of unique SMO mutations (Table 1; Figure 3) and occurrence of compensatory mechanisms that confer resistance to this drug (see below) [65,97]. Here, SMO is linked to skin basal cell carcinoma.