To evaluate the prognostic factors of unknown primary head and neck squamous cell carcinoma (HNSCC).Retrospective study.Patients with unknown primary HNSCC from 1980 to 2000 were included.Forty-eight patients, predominantly male and with a mean age of 63.3 ± 11.6 years, were recruited. The median survival time (MST) was 44 months. The overall survival rate was 60.4 percent at three years and 39.6 percent at five years. Forty-two patients receiving intervention regimens had a MST of 45 months, while six patients receiving palliative therapy had a MST of 8.5 months (log rank test, P = 0.016). With multivariate Cox regression analysis, age (per year), higher nodal stage (N3 vs N1 or N2), and treatment (operation vs nonoperation) had a hazard ratio of 1.081 (P < 0.0001), 5.852 (P = 0.010), and 0.4 (P = 0.042), respectively.Older age, higher nodal stage, and palliative treatment indicated poor prognosis. Survival time might be prolonged if surgical treatment is tolerable.