Recent reports from US and Japan have established that mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (Egfr) occur in a subset of patients with lung cancer that respond to therapy with gefitinib, a TK inhibitor. To gain further insights into the role of Egfr in carcinogenesis of lung and tumors of diverse histology, that are currently under investigation with drugs of the same class, we have taken in examination a panel of tumors consisting in 110 pulmonary adenocarcinomas, 40 pulmonary squamous carcinomas, 40 gastric adenocarcinomas and 40 colorectal adenocarcinomas. The sequence analysis of exon 19 and 21 of the Egfr has allowed the identification of 10 cases exhibiting specific deletions in exon 19 and 1 case with point mutation in a conserved residue in exon 21. All Egfr mutations occur specifically in lung adenocarcinomas while tumors of different histology result unaffected. The rate of mutation affecting these other tumors is either very rare, involves different domains of the receptor or other tyrosine kinases. The molecular analysis of the Egfr gene can help identify patients that will benefit from gefitinib therapy.