Neuroblastic tumors (NTs) are the most common extracranial solid tumors in children. Topoisomerase (DNA) II alpha (TOP2A) is a critical nuclear enzyme involved in DNA replication and mitosis, which is targeted by several chemotherapeutic agents. To date, little is known about the expression of TOP2A in neuroblastic tumors. This study was conducted to evaluate TOP2A protein expression and TOP2A gene alteration, as well as its prognostic value in neuroblastic tumors. We analyzed 88 cases of NTs with immunohistochemistry for protein expression, and 80 cases using fluorescence in situ hybridisation (FISH) for gene status of TOP2A. Statistical analyses were performed to evaluate the correlations between TOP2A expression and the clinicopathological characteristics of the patients as well as the predictive value of TOP2A. The results showed that TOP2A protein was expressed in 59.09% of NTs, and 23.86% of NTs showed high TOP2A expression in > 50% of tumor cells. The high expression of TOP2A was significantly linked to aggressive NT type (P=0.006), and also strongly correlated with high Ki-67 index (P= 0.000) and mitosis-karyorrhexis index (MKI) (P= 0.001). TOP2A amplification was found in 35.00% of NTs and was more frequently detected in the advanced clinical stage neuroblastomas (stage III and IV) (P=0.028), older patients (> 18 months) (P= 0.000) and high risk cases (P= 0.001). It was discovered that the TOP2A gene amplification did not correlate with protein overexpression. Survival analyses showed that high TOP2A protein expression was significantly associated with worse survival (P= 0.005). Multivariate analyses demonstrated that TOP2A expression was an independent predictive factor for poor prognosis (P= 0.010). In summary, high TOP2A protein expression was more frequently found in aggressive type of NTs, and in cases with high Ki-67 index or high MKI. TOP2A amplification was more frequently presented in late stage neuroblastomas, older patients (> 18 months) and high risk group. Furthermore, TOP2A protein expression was significantly associated with shorter survival. It is therefore concluded that TOP2A protein expression is an independent unfavorable predictive factor in NTs.