OBJECTIVES: To evaluate the impact of clinical, histopathological, and molecular biological parameters on the prognosis of nasopharyngeal carcinoma (NPC). STUDY DESIGN AND SETTING: The clinical records of 48 patients with a diagnosis of NPC were retrospectively reviewed. In situ hybridization for Epstein-Barr virus encoded small RNA I (EBER-ISH) was applied for 30 paraffin-embedded specimens available. Prognostic factors of NPC were meticulously analyzed. RESULTS: The EBER-ISH signal was shown to be highly significant as a favorable prognostic factor (P = 0.007). Although EBV was more commonly associated with Type III NPC, EBERISH-positive Type I-II NPC had also significantly better survival rate than EBER-ISH-negative Type I-II NPC (P = 0.036). CONCLUSIONS: In addition to the WHO histopathological grade, the 1997 UICC staging, nodal status, and distant metastasis at presentation, the EBER-ISH signal was shown to be significant as a prognostic factor. SIGNIFICANCE: This is the first report to describe the EBERISH as an independent prognostic factor of NPC regardless of histopathology.