Medulloblastomas and related primitive neuroectodermal tumors are the second most common malignant tumors of childhood. In spite of improvements in cancer therapy, these tumors are still associated with significant morbidity and mortality. Although these tumors share similar histologic features, recent molecular studies suggest that they could represent a genetically mixed group of tumors. The genetic events that might play a role in the biology of these tumors also could allow a molecular subtyping of medulloblastomas. Such molecular subtyping of medulloblastomas could allow for the use of newer therapeutic techniques, such as gene therapy, for selective targeting of critical genetic events in subsets of medulloblastomas. It is becoming increasingly clear that in medulloblastomas, the morphologic similarity of "small blue" cells does not imply similar or shared molecular characteristics, with implications for differing tumor biology.