In high‐risk neuroblastoma (HR‐NB), the clinical significance of long‐term minimal residual disease (MRD) monitoring using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) for neuroblastoma mRNAs has not been investigated. We report long‐term MRD follow‐ups of four patients with HR‐NB throughout the disease (diagnosis, remission, and relapse) and treatment course (chemotherapy, autologous and allogeneic stem cell transplantation, and donor lymphocyte and natural killer cell infusions). The results showed the stability of mRNA marker expression after different treatments and demonstrated their validity to predict relapse and assess therapeutic response. This opens up the possibility of investigating the utility of long‐term molecular monitoring of MRD in prospective multicenter studies.