Mutations of the epidermal growth factor receptor (EGFR) gene are known to be associated with the pronounced tumor response to EGFR tyrosine kinase inhibitors (TKI). Unfortunately, these TKI-sensitizing alterations have been detected almost exclusively in lung adenocarcinomas; indeed, their occurrence in tumors of other histologic types or other organs is exceptionally rare. Here we report a case of intragenic EGFR microdeletion in renal cell carcinoma (RCC) associated with the effect of treatment by gefitinib. Patient G., 60 years old, underwent radical surgery for clear cell RCC, however local relapse and metastatic lesions in the lungs were revealed 33 months later. The patient was successfully treated by interleukin-2 (first line therapy), tamoxifen (second line), and interferon-alpha (third line). After disease progression, EGFR mutation test was performed as a compassionate attempt. It revealed "classical" 15 base pair deletion, so gefitinib was administered. This treatment led to a dramatic symptomatic response within the first week of therapy; reduction of dyspnea was so evident that it allowed the patient to return to work. Clinical examination demonstrated significant improvement with respect to pleuritis and pericarditis. The duration of tumor response, which was classified as disease stabilization, was equal to 4 months. This case report suggests that kidney tumors have to be investigated more closely with respect to the occurrence of TKI-sensitizing EGFR mutations.