The discovery of microRNAs (miRNAs) has opened a new avenue for both diagnosis and treatment of cancers. Accumulating experimental evidences indicate that miRNAs are aberrantly expressed in different tumor types and have a critical role in tumorigenesis. However, the miRNA expression profile in neuroblastoma (NB), one of the most common cancer forms in children, has not been well characterized. In the present study, we established a heterotopic transplant mice model of NB and employed miRNA microarray analysis to identify miRNAs that are differentially expressed in metastatic NB compared to primary NB. A list of 54 miRNAs was found to be significantly altered in metastatic tumors compared to primary tumors. These differentially-expressed miRNAs were selectively validated by a stem-loop qRT-PCR assay. Furthermore, we predicted a list of potential miRNA-target pairs that may be involved in the metastasis of neuroblastoma by three different computer-aided algorithms. Taken together, our results indicate that a unique panel of miRNAs are associated with metastatic NB and these differentially-expressed miRNAs may play an important role in the NB metastatic process. This finding may also shed light in our understanding of the nature of metastatic NB and provide a potential novel target for therapeutic treatment of this tumor.