Since we recently demonstrated the up-regulation of both DNMT3A and DNMT3B transcript levels in RMS tumour samples compared to normal skeletal muscle and the antitumoral effects of DNMT3B knocking down on ERMS cell lines [25], here, we analysed DNMT3A/3B involvement in radioresistance mechanisms. The gene discussed is DNMT3B; the disease is embryonal rhabdomyosarcoma.