ETV6/TEL, a member of the ETS family of transcription factors, has been involved in a variety of gene fusions in various neoplasms. One of its fusion partners is NTRK3/TRKC, which encodes the receptor for neurotrophin-3. Although NTRK3 is expressed broadly in neural tissues during the growth and development of the central nervous system, its fusion with TEL has never been reported in central nervous system tumors. We report here a new TEL–NTRK3 fusion in a primitive neuroectodermal tumor (PNET). The patient was five months old when she underwent a resection of a left frontal tumor that was diagnosed as a benign desmoplastic infantile ganglioglioma. Three months later she had another resection for the recurrent tumor, which was diagnosed as a highly malignant PNET. G-banding karyotype analysis showed 46, XX in both tumors, but spectral karyotyping revealed a single near-tetraploid cell in the first tumor with a t(12; 15)(p13; q25) translocation and the same translocation in all metaphases in the PNET. Subsequent fluorescence in situ hybridization analysis using a TEL probe revealed the translocation of the TEL gene to the der(15) chromosome. Based on a similar translocation previously described in infantile fibrosarcoma, congenital mesoblastic nephroma and acute myeloid leukemia involving the TEL and NTRK3 genes, we used the polymerase chain reaction with reverse transcription, with primers flanking the coding sequences of TEL and NTRK3, to detect a chimeric message of 1.6 kilobases. We located the breakpoint at the end of exon 4 of TEL in frame with exon 12 of NTRK3. This results in a unique TEL–NTRK3 fusion transcript with the helix–loop–helix dimerization domain of TEL fused to the protein tyrosine kinase domain of NTRK3. Since t(12; 15) is the only structural chromosome aberration in this case and a similar TEL–NTRK3 fusion product has been used to transform NIH 3T3 cells, we propose that the TEL–NTRK3 fusion may have contributed to the cellular transformation and progression of this tumor.