Objectives/Hypothesis: To determine if there is a difference in overall survival, cause-specific survival, and relapse-free rate between young patients (<40 years of age) with head and neck squamous cell carcinoma (HNSCC) and older patients (>40 years of age). Study design: A matched control study describing the outcome of 185 previously untreated HNSCC patients less than 40 years of age treated at the Princess Margaret Hospital, Toronto, Ontario, Canada, between 1958 and 1992. The young patient group was compared with a control group of older patients (> 40 years of age) which was selected randomly from an entire cohort of patients (n = 10,072) and matched for site, sex, and date of presentation. Methods: The medical records were reviewed and data abstracted for demographic information, tobacco and alcohol use, family history, primary site, clinical stage, primary treatment, histology, the occurrence of residual or recurrent disease, salvage treatment, development of subsequent primaries, survival, and the eventual cause of death. The patient's TNM stage was reclassified according to American Joint Cancer Committee/Union Internationale Contre le Cancer (AJCC/UICC) 1992 criteria on the basis of the initial clinical description and staging investigations. A multivariate regression analysis was performed. To assess the importance of age as a prognostic factor for survival, the Cox proportion hazard model was used. Smoking status was also tested in the stratified Cox proportional hazard model. Results: Tumor stage and treatment modalities were comparable in both groups. The 5-year, cause-specific survival in both groups was not statistically different (72% vs. 68%, P = .91). The young patient group had a significantly better 5-year overall survival compared with the older patient group (68% vs. 49%, P = .0011). Older patients developed more subsequent primary neoplasms than the younger patient population (18% vs. 8%, P = .005). There were significantly more females, an increased incidence of oral or oropharyngeal cancer, and fewer smokers in the young patient group. Smoking, however, had an important impact on outcome with all but one patient who developed a second primary in the upper aerodigestive tract having smoked. Multivariate analysis showed that only disease stage and cancer site were significant prognostic factors for survival. Conclusions: Young patients with HNSCC do not have a worse prognosis than a matched older patient group in this case-controlled study (power > 0.75 for a minimal detectable difference of 10% disease-free survival between the two groups).