Medulloblastoma is the most common malignant brain tumor in childhood. The most prevalent chromosomal abnormalities are isochromosome 17q and loss of 17p, the location of the tumor suppressor gene p53. Mutations in the p53 gene in medulloblastoma are relatively infrequent but have recently been correlated to poor prognosis. Furthermore, the p53 gene encodes nine different isoforms, which may have a profound impact on p53 tumor suppressor activity. Nine medulloblastoma primary biopsy samples, six cell lines from medulloblastoma, and one from a supratentorial PNET, and a medulloblastoma xenograft, along with human brain and visceral tissues, were analyzed by Western blotting, using monoclonal p53 antibodies against two regions in the N-terminus or the central domain. Medulloblastoma primary tissue and xenografts present low molecular weight proteins recognized by both N-terminal p53 antibodies that are absent in all cell lines including the one used for xenografts. Normal visceral organs display short forms of p53, and low levels of canonical p53. Normal brain structures, including cerebellum, contained only canonical size p53 at high levels. In conclusion, our results indicate that the presence of p53 isoforms may play a functional role in medulloblastoma. The observed differences in their presence in cell lines and derived xenografts, suggest that p53 should be investigated in in vivo models rather than in cell lines.