Despite intensive high-dose chemotherapy and autologous hematopoietic stem cell transplantation, disseminated neuroblastoma (NB) frequently proves to be chemosensitive but not chemocurable, and more often so in NB-presenting MYCN amplification. To assess the direct relationship between the MYCN oncogene and chemoresistance acquisition during NB metastatic dissemination, we have studied MYCN and MDR1 genes using the human IGR-N-91 ectopic xenograft metastatic model. This characterized experimental in vitro model includes human neuroblasts derived from a subcutaneous primary tumor xenograft, disseminated blood cells, myocardium, and bone marrow (BM) metastatic cells. All IGR-N-91-derived neuroblasts harbor a consistent MYCN genomic content but, unlike primary tumor xenograft, BM, and myocardium, human neuroblasts elicit a concomitant increase in MYCN and MDR1 transcripts levels, consistent with chemoresistance phenotype and active P-gp. In contrast, no variation of MRP1 transcript level was associated with the metastatic process in this model. Using an MDR1 promoter-CAT construct, we have shown that the MycN protein activates MDR1 transcription both in exogenous transient MYCN- Neuroblastoma (NB), the most common solid tumor of early childhood, originating in tissues of the sympathetic nervous system, presents extreme heterogeneity clinically, histologically, and genetically. From a clinical point of view, NBs are classified according to stage (localized stages 1, 2, and 3, and metastatic stage 4) and the child's age at diagnosis (Ͻ1 year and Ͼ1 year). On presentation, stage-4 NBs systematically present involved bone marrow (BM). From a biological point of view, following cytogenetic and genetic research throughout the past 2 decades, NB tumors can be classified into three types depending on genomic and genetic alterations.