The diagnosis of any tumor is based on morphology and genetic analysis which is only possible by biopsy. However, it is not always feasible to obtain tissue tumor biopsy due to its invasive nature. Also, the tumor heterogeneity and minimal residual disease (MRD) will remain undetected. To overcome these problems, liquid biopsies can be a non-invasive alternative. Circulating tumor DNA (ctDNA) in liquid biopsies from patients with cancer can be used for diagnostic and prognostic purposes. The level of ctDNA at diagnosis correlates with tumor burden. Liquid biopsies also overcome the problem of spatial or (sub)clonal tumor heterogeneity, facilitating increased diagnostic accuracy and enabling MRDs detection and therapy response monitoring. Furthermore, ctDNA offers the opportunity to investigate clonal evolution of the tumor and possible distant lesions throughout the body at several time points during treatment. We aim to translate ctDNA-based sequencing approaches of liquid biopsies into pediatric patients – specifically, those with solid tumors.