We examined 22 cases of renal-cell carcinoma (RCC) for structural alterations of the epidermal growth factor receptor (EGFR) gene and found gene amplification in one case of high-stage-high-grade RCC. Dot blot analysis of the total RNA from tumorous and normal kidney tissues revealed overexpression of the EGFR gene in 12 of 20 (60%) cases of RCC. The highest expression was observed in the gene-amplified case. No correlation was observed between the level of EGFR mRNA and tumor stage or grade. Northern blot analysis revealed normal 10- and 5.6-kb EGFR mRNA bands in RCC. Our data indicate that gene amplification of the EGFR gene is one of the molecular mechanisms of its overexpression in a subset of RCCs.