AbstractAs a sympathetic nervous system–derived tumor, aggressive neuroblastoma (NB) is currently attracting interest from researchers seeking diagnostic and prognostic markers via less invasive procedures. The analysis of circulating tumor DNA (ctDNA) in peripheral blood can provide genetic information from multiple tumor lesions and is not dependent on a surgical procedure. The identification of genetic alterations, chromosomal variations, and hypermethylation contained within plasma DNA yields clinical value in the diagnosis, risk stratification, monitoring of treatment effects, and survival prediction for patients. With the widespread application of genome sequencing, droplet digital polymerase chain reaction, and other advanced technologies, the detection of ctDNA may guide therapeutic schedules, enhance the quality of life, and improve the prognosis for patients with NB.