Neuroblastoma (NB) is cancer formed in the nerve tissue, frequently originating in the adrenal glands. This malignancy is responsible for 15% of deaths worldwide. At the time of diagnosis, 73% of NB patients have already developed malignant lesions outside the primary tumor. Furthermore, children diagnosed with malignancy after 18 months of age have frequently metastatic tumors. The clinical hallmark of NB is the heterogeneity, featuring outcomes ranging from lethal progression to spontaneous regression, and depending upon its severity is classified in different risk groups. High-risk NBs occurring in children over 18 months of age are commonly metastatic, require intensive multimodality therapy, and are associated with a 40-50% survival rate. In our research, we have found that tumor-cell populations differ between low- and high-risk NBs. Notably, a population of progenitor cells that exist in the postnatal adrenal gland with migratory and mesenchymal-like signatures is common to high-risk tumors but absent in favorable malignancies. How are different types of cells and stem-like properties associated with metastasis? Can we trace the cellular and molecular evolution from primary tumors to metastatic lesions? With the present project, we aim to answer both questions. Identifying the molecular mechanism and cell origin of metastasis and chemotherapy resistance can unlock new strategies for the early diagnosis and treatment of high-risk, poor-outcome metastatic NB. The results of this project will provide invaluable information to diagnose and treat NB, particularly the most severe and lethal forms of malignancy. In addition, it will help to elucidate the cellular and molecular origins of metastasis and to clarify the role of mesenchymal-like cells in drug resistance. Furthermore, the software developed as part of the project will allow investigating the evolution of other types of cancers. These achievements will improve the life quality of children with NB in Sweden and around the world.