The transmembrane proto‐oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system. Here, we report the fusion of its carboxy‐terminal kinase domain to the amino‐terminal portion of a protein called FIG (Fused in Glioblastoma) in a human glioblastoma multiforme (GBM). By characterizing both FIG and ROS genes in normal and in U118MG GBM cells, we determined that an intra‐chromosomal homozygous deletion of 240 kilobases on 6q21 is responsible for the formation of the FIG‐ROS locus. The FIG‐ROS transcript is encoded by 7 FIG exons and 9 ROS‐derived exons. We also demonstrate that the FIG‐ROS locus encodes for an in‐frame fusion protein with a constitutively active kinase activity, suggesting that FIG‐ROS may act as an oncogene. This is the first example of a fusion RTK protein that results from an intra‐chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma. © 2003 Wiley‐Liss, Inc.