Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were separately found associated with prognosis in adult patients with nasopharyngeal carcinoma (NPC). To date, their expression patterns and prognostic utility have never been specifically addressed in children and adolescents. Thirty consecutive NPC patients aged<or==20 years and treated by radiotherapy (RT) with (n=14) or without (n=16) systemic chemotherapy (CT) were accrued between 1988 and 2001 in a single institute. The clinical outcomes were correlated with clinicopathological features in 30 patients and with immunostains of EGFR and COX-2 in 20 patients with available blocks. The 5-year rates of overall survival (OS) and disease-free survival (DFS) were both 76.4%. Overexpression of EGFR and COX-2 was identified in 13 (65%) and 14 (70%) cases, respectively. The expression levels of these two oncoproteins did not significantly correlate with each other, DFS, OS, and any of clinicopathological factors, including histological subtype, AJCC stage, T stage, and N stage. The only significant prognosticator predictive of adverse outcomes was AJCC stage IV at presentation, which, compared with lower-staged diseases, decreased the rates from 85.2% to 55.6% at 5 years for both DFS (p=0.05) and OS (p=0.05). Despite lacking significant prognostic values, EGFR and COX-2 were overexpressed in approximately two-thirds of pediatric NPC. Such high frequencies provide the basis of combined targeted therapy by specific pharmacological inhibitors to enhance the effects of RT and CT. However, it requires further investigation on the difference between pediatric and adult NPC patients in clinical and biological implications of EGFR and COX-2.