In this study, we demonstrated that the ubiquitin E3 ligase RNF5, an endoplasmic reticulum (ER) ubiquitin ligase implicated in ER-associated degradation of misfolded proteins, was expressed in NB and melanoma patients and that its expression positively correlated with better clinical outcome in terms of overall and event-free survival. Here, RNF5 is linked to neuroblastoma.