Medulloblastoma (MB), the most frequent malignant brain tumor in children, is localized in the cerebellum. The standard care includes surgery, radiotherapy and chemotherapy leading to an overall survival (OS) of 70-80% but survivors suffer from severe side effects. Based on gene expression, MB is divided in four different molecular subgroups: WNT, SHH, Group 3 (G3) and Group 4 (G4), which differ in terms of clinics, prognosis, genetic alterations and cell of origin. The WNT group is characterized by the activation of the WNT/β-catenin signaling pathway and displays the best prognosis. The SHH group is driven by deregulation of the SHH signaling pathway and has an intermediate prognosis. G3 and G4 are less characterized. In contrary to the SHH and WNT groups, no specific alteration of a given signaling pathway has been described. G3 is the group with the worse prognosis. Few recurrent genetic alterations have been characterized including MYC amplification in less than 20% of G3 tumors. Nevertheless, all G3-MBs overexpress MYC through mechanisms not completely understood. G3-MB also express an abnormal photoreceptor differentiation program found in the retina but not in the cerebellum during normal development. It has been shown that NRL and CRX, two master transcription factors (TF) of the photoreceptor lineage, are required for the establishment this program as well as for G3 tumor maintenance. G4 has an intermediate prognosis and the most frequent alteration is the overexpression of PRDM6. It has been recently proposed that this group could be driven by activation of an ERBB4-SRC signaling.Established cell lines and patient-derived xenografts (PDXs) are available to study MB. The different groups of MB have also been modeled in vivo using either genetically engineered mouse models (GEMM) or by orthotopic transplantation of mouse cerebellar progenitors modified to overexpress oncogenes and/or to inactivate tumor suppressors. Here, we provide the readers with tools and information that allow MB modeling in vivo. We describe how to purify granular cell cerebellar progenitors or PDXs and to culture them in vitro in order to modulate gene expression by lentiviral infection. We provide protocols for the retrovirus production and infection. We also describe the experimental procedures for orthotopic grafting in the cerebellum, which is used to assess how genetic modifications alter in vivo tumor formation of reinjected modified PDXs cells or GCPs.