Pleomorphic xanthoastrocytoma (PXA) is a rare cerebral tumor of young adults with a slow growth and a good prognosis. Due to its peculiar histopathological findings, the tumor resemble to the lytic phase of progressive multifocal leukoencephalopathy (PML), a JC Virus (JCV) induced disease. For these reasons, the presence of JCV genoma and viral particles were searched for by means of nested polymerase chain reaction (nPCR) and electron microscopy (EM) in a 9-year-old child with PXA. Although EM did not reveal any viral particles, nPCR did reveal genomic sequences of the LT, R, and VP1 regions of JCV. Sequence analysis showed that the R region was mutated with respect to the archetypal form thus yielding the Mad 4 variant of JCV previously reported as being oncogenic in animals. We suggest that JCV may have played a role in the development of this tumor.