This case report describes the effects of long-term treatment with the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib ('Iressa', ZD1839) on a patient with squamous cell carcinoma of the lung. Gefitinib is an orally active agent that blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and host-dependent processes that promote tumor growth. A 62-year-old Japanese man with a history of heavy smoking was diagnosed with squamous cell carcinoma of the lung, clinical stage IIIB (T4N3M0), in August 2000. He received two cycles of cisplatin-based chemotherapy and subsequently underwent left upper lobectomy followed by thoracic radiotherapy. After these treatments, he underwent partial lobectomy and pneumonectomy because of disease recurrence. In June 2002, he started treatment with gefitinib 250 mg/day orally because of mediastinal lymph node recurrence and an elevated serum cytokeratin 19 fragment (CYFRA) level. As a result, the mediastinal lymph node markedly regressed and the serum CYFRA level became normalized. Although he experienced recurrence three times during the 18 months prior to treatment with gefitinib, recurrence has not been experienced in the 13 months since the start of gefitinib treatment, while tolerability has been acceptable.