In conclusion here we demonstrate that in the three NB cell lines, the RA-dependent Ret activation, both if GDNF-mediated (SK-N-BE) or TrkB-mediated (SH-SY5Y and LAN-5) is needed to induce cell differentiation since the outcome of blocking Ret phosphorylation is a failure in NB cell differentiation. This evidence concerns the gene GDNF and neuroblastoma.