We analyzed all 21 exons of the RET proto-oncogene of paired genomic DNA from tumors and normal tissues in 12 small cell lung cancer (SCLC) patients for the presence of genetic alteration. Polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing revealed that heterozygosity of the RET proto-oncogene was lost in the tumor tissues of six patients out of eight informative SCLC patients, although point mutation was not evident in any tumors. These results suggest that a deletion of the chromosomal region including the RET proto-oncogene is involved in the pathogenesis of SCLC. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.