Cytogenetic analysis of peripheral primitive neuroectodermal tumors (PNETs) has demonstrated a consistent primary chromosomal change characterized by a reciprocal translocation t(11;22)(q24:q12). In the central nervous system PNETs, most frequent of which are the cerebellar medulloblastomas, the most prevalent chromosomal abnormalities include deletions and unbalanced translocations. The recent cloning of the t(11;22) breakpoint has revealed the fusion of the human FLI-1 gene on chromosome 11q24 with a gene EWS on chromosome 22q12 and permitted detection of fusion transcripts. Molecular genetic analysis for the presence of EWS/FLI-1 fusion transcripts by the reverse transcriptase-polymerase chain reaction has recently been applied to peripheral PNETs. In the present study, we analyzed eight central PNETs by reverse transcriptase-polymerase chain reaction for EWS/FLI-1 fusion transcripts. The tumors included six PNETs of the cerebellum, one supratentorial PNET of the frontal lobe and one PNET of the pineal region. Polymerase chain reaction analysis in all eight cases failed to reveal a t(11;22) translocation indicating that this is not a cytogenetic abnormality of the central PNETs. Reverse transcriptase-polymerase chain reaction analysis of EWS/FLI-1 fusion transcripts provides a novel adjunctive tool in the differentiation of central versus peripheral PNET.