Medulloblastoma (MB) is the most common type of brain tumor affecting children. These tumors are a significant cause of childhood mortality and morbidity, and more effective and less invasive treatment options are urgently required. To achieve these aims, it will be critical to develop a more comprehensive understanding of the molecular pathogenesis of MB. At present, there are relatively few well-characterized MB cell lines available to the research community for the study of MB molecular and cellular biology. Here we present the case reports of two children diagnosed with classic and desmoplastic MB, and describe the characteristics of two new MB cell lines derived from these individuals. A number of genes encoding components of the sonic hedgehog (SHH) and WNT pathways were up-regulated in the desmoplastic relative to the classic MB cell line consistent with aberrant activation of these pathways in desmoplastic MB. These cell lines represent an additional resource for the analysis of diverse aspects of MB biology.