The use of Smo inhibitors for the treatment of medulloblastoma is being tested in the clinic with encouraging results (Robinson et al, 2015), but could be significantly prevented by the acquisition of resistance through secondary Smo mutations, described in basal cell carcinoma and medulloblastoma (Yauch et al, 2009; Atwood et al, 2015; Sharpe et al, 2015). Here, SMO is linked to medulloblastoma.