The presence of Epstein–Barr virus (EBV) genomes in the DNA of tumor cells of undifferentiated carcinoma of nasopharyngeal type (UCNT), associated with significant lymphocytic infiltration of tumor led to therapeutic trials with interferon (IFN) because of its antiviral, antiproliferative, and immunomodulatory properties. Fourteen patients with histologically proven UCNT (2 had locoregional disease alone and 12 metastatic disease) who were refractory to conventional chemotherapy, were treated with IFN gamma 20 × 106 U twice a week. Treatment was well tolerated. No objective response were achieved in the 13 evaluated patients, and all patients progressed after a median treatment duration of 10 weeks (6–32). IFN gamma seems unable to induce antitumor activity alone in such heavily pretreated patients. Its possible place in the management of UCNT is probably earlier in the natural history of this disease.