CD271 signaling pathways are very variable depending on the different tissues that they operate in and the ligands that bind to the receptor, but recent studies have shown that CD271 could determine the migratory and proliferative properties in melanoma and HNSCC through the activation of Ras homolog gene family member A (RhoA), Jun kinase (JNK), and nuclear factor kB (NF-kB) pathways [11,12,13,14,15,16,17]. This evidence concerns the gene RHOA and head and neck squamous cell carcinoma.