Comorbidities often contraindicate any chemotherapy in non-small cell lung cancer (NSCLC) patients, even single-agent one. This is the case of chronic renal failure.Two elderly patients (age >70 years) affected by advanced non-small cell lung cancer and chronic renal failure were treated, as front-line treatment, with gefitinib (ZD1839 – ‘Iressa’) administered orally at the dose of 250mg daily.In both patients renal function was not impaired by the treatment with gefitinib and no severe toxicity was recorded. One patient reported a stable disease, lasted 141 days, with symptoms relief. In the other patient a mixed response was reported with one large pulmonary site responding to gefitinib, but with appearance of new small lung metastases. He is still alive at 359 days.Gefitinib resulted safety when administered to advanced NSCLC elderly patients affected by chronic renal failure. Gefitinib should be further evaluated as front-line treatment in a larger sample of such patients, in order to establish a therapeutic option for a sort of patients unsuitable for any chemotherapy.