Objective To investigate the predictive value of mRNA expression of five neuroblastoma (NB) markers—chromogranin A, doublecortin, dopa decarboxylase, paired-like homeobox 2b, and tyrosine hydroxylase (collectively referred to as NB5)—in bone marrow (BM) and peripheral blood (PB) for metastasis and recurrence in pediatric NB, to compare its performance with conventional flow cytometric measurable residual disease (MRD) detection, and to analyze its correlation with progression-free survival (PFS). Methods Clinical data of 47 children with NB admitted to Hunan Provincial People's Hospital from October 2018 to December 2024 were retrospectively collected. Real-time quantitative reverse transcription-polymerase chain reaction was used to detect NB5 expression in BM and PB. Survival was analyzed by the Kaplan-Meier method, and multivariable Cox regression was performed to adjust for confounders. Results A total of 47 children were enrolled, including 44 high-risk (94%) and 3 low-risk (6%) patients. Overall, 99 BM tests were completed. The BM-NB5 positivity rate was 31% (31/99), significantly higher than the MRD positivity rate (19%, 19/99) and the BM morphologic positivity rate (15%, 15/99) (both P<0.001). Among 19 paired BM-PB samples, PB-NB5 was positive in 4 cases and BM-NB5 was positive in 8 cases; the positive concordance rate was 100%, the negative concordance rate was 47%, and the kappa coefficient was 0.321 (weak agreement). Log-rank analysis showed that among MRD-negative patients, the NB5-positive group had significantly shorter PFS than the NB5-negative group (P=0.040). Cox regression indicated a marginal association between NB5 expression and PFS (HR=4.367, 95%CI: 0.896-21.277, P=0.068). Conclusions BM-NB5 detection shows superior sensitivity for MRD identification compared with flow cytometric MRD and BM morphology in high-risk NB patients and can provide early warning of recurrence risk. NB5 expression appears to stratify prognosis in NB, warranting validation in a larger cohort to confirm its independent prognostic value.