Neuroblastoma is the most common extracranial solid tumor in children, and the overall survival rate of patients in the high-risk group is less than 50%. Circulating tumor cells have recently been found to be a potential source of tumor progression, metastasis, and poor prognosis in patients with cancer. There is a dearth of data on the malignant potential of circulating tumor cells in neuroblastoma. Therefore, in this article, we briefly review the methods of quantifying circulating neuroblastoma cells and the relationship between the presence of many circulating tumor cells and prognosis for patients with neuroblastoma. The relationship between higher numbers of circulating neuroblastoma tumor cells and poor prognosis was outlined. However, the data in most studies represented only the tumor burden, and there is no direct evidence that circulating tumor cells are the source of tumor progression and metastasis in patients with neuroblastoma. A comprehensive genetic analysis of circulating tumor cells, including single-cell sequencing and functional assays using ex vivo cell culture and xenografts, may provide insights into the malignant nature of neuroblastoma.Neuroblastomas are the most common type of extracranial solid tumor in children, accounting for ~13% of all pediatric malignancy-related deaths (1). Neuroblastomas are characterized by wide clinical heterogeneity that results in varied clinical presentations, ranging from spontaneous regression to aggressive progression. The overall survival rate of patients in the high-risk group is less than 50% (2).Circulating tumor cells (CTCs) passively or actively migrate into the blood from primary tumor sites and metastases. Most CTCs die in the blood due to shear stress, anoikis, and immune reactions, but subgroups of CTCs have a metastasis-initiating capacity (3-5). Epithelial-mesenchymal transition (EMT) is a well-known biological mechanism associated with CTCs, and EMT in tumors has been associated with metastasis and poor prognosis (4) (Figure 1). This review focused on the malignant biology and prognostic value of CTCs in neuroblastoma. Moreover, future perspectives on the molecular analysis of CTCs in neuroblastoma are also discussed.