The study investigates the role of the proto-oncogene *MYCN* in neuroblastoma development by creating transgenic mice that overexpress *MYCN* in neuroectodermal cells. The tumors developed in these mice exhibit histological features consistent with human neuroblastomas, including neuronal differentiation, ganglionic elements, and synaptophysin and neuron-specific enolase staining. Comparative genomic hybridization (CGH) analysis revealed chromosomal gains and losses in the transgenic tumors that are syntenic with those observed in human neuroblastomas. The results demonstrate that *MYCN* overexpression can initiate neuroblastoma in mice, suggesting that *MYCN* contributes to neuroblastoma genesis. Additionally, the study found that increased dosage of *MYCN* or deficiencies in tumor suppressor genes *NF1* or *RB1* further augment tumorigenesis. These findings provide direct evidence for the role of *MYCN* in neuroblastoma and suggest that genetic events involved in neuroblastoma development can occur in multiple chronological sequences. The transgenic mouse model developed in this study may be useful for identifying additional genes involved in neuroblastoma and for testing new therapies.The study investigates the role of the proto-oncogene *MYCN* in neuroblastoma development by creating transgenic mice that overexpress *MYCN* in neuroectodermal cells. The tumors developed in these mice exhibit histological features consistent with human neuroblastomas, including neuronal differentiation, ganglionic elements, and synaptophysin and neuron-specific enolase staining. Comparative genomic hybridization (CGH) analysis revealed chromosomal gains and losses in the transgenic tumors that are syntenic with those observed in human neuroblastomas. The results demonstrate that *MYCN* overexpression can initiate neuroblastoma in mice, suggesting that *MYCN* contributes to neuroblastoma genesis. Additionally, the study found that increased dosage of *MYCN* or deficiencies in tumor suppressor genes *NF1* or *RB1* further augment tumorigenesis. These findings provide direct evidence for the role of *MYCN* in neuroblastoma and suggest that genetic events involved in neuroblastoma development can occur in multiple chronological sequences. The transgenic mouse model developed in this study may be useful for identifying additional genes involved in neuroblastoma and for testing new therapies.