Despite the efforts dedicated to this pathway in RMS, the activation mechanism remained elusive, probably caused by the fact that the expression of the most commonly studied ligand of the pathway, the Sonic Hedgehog protein (SHh) is very often negligible in RMS tumours (more than 75% of samples showed no detectable SHh expression) and the prominent expression of the two alternative ligands (Indian (IHh) and Desert (DHh) Hedgehog) was almost always left aside in previous cancer studies. This evidence concerns the gene SHH and neoplasm.