SMO (smoothened, frizzled class receptor) is a G-protein coupled receptor and member of the Hedgehog signaling pathway, which is involved in cell fate, proliferation, and survival. Simple variants in SMO are seen in about 1% of all tumors, including 3% of skin and colorectal tumors. SMO gain-of-function mutations are associated with basal cell carcinoma. SMO variants may predict resistance to certain HH-pathway inhibitors in basal cell carcinoma.