Background This single‐center, phase II study assessed the safety/tolerability and initial efficacy of gefitinib in patients with nasopharyngeal carcinoma (NPC) pretreated with platinum‐based chemotherapy. Methods Patients with recurrent and metastatic NPC who had treatment failure with at least 2 lines of chemotherapy including platinum were given gefitinib at a fixed dose of 250 mg daily. Treatment was continued until the patient experienced unacceptable side effects or disease progression. Results Nineteen patients were enrolled, having had treatment failure with a median of 2 chemotherapy regimens. Treatment was well tolerated, and only grades 1 to 2 adverse events were observed. None of the patients achieved partial or complete response. Median time‐to‐progression was 4 months, and median overall survival was 16 months. Conclusion Gefitinib was well tolerated, but the response rate was poor in this heavily pretreated study population, and its use in NPC is not recommended outside the context of clinical trial. © 2008 Wiley Periodicals, Inc. Head Neck, 2008