Immunostaining using an affinity-purified rabbit polyclonal antibody against the extracellular domain of the epidermal-growth-factor receptor (EGFR) showed over-expression occurring in a fraction of tumor cells in 17 out of 18 human glioblastomas and in a majority of cells in 7 of the 18. Southern-blotting technique using a full-length EGFR cDNA probe showed a variable degree of amplification in 10 of the 17 glioblastomas, which was associated with EGFR over-expression in each case. In 2 of the glioblastomas with EGFR gene amplification, a rearrangement of the gene affecting the extracellular domain of the receptor was identified and DNA sequence analyses revealed an identical deletion-rearrangement of 801 base pairs between exons 2 to 7, resulting in an in-frame fusion of exons 1 and 8.