Background: Despite the advances in diagnostic imaging and treatment modalities, the risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Cell adhesion molecules play critical functional roles in the cross talk with tumor microenvironment to implicate carcinogenesis. Focusing on cell adhesion-associated genes, we performed data mining from published NPC transcriptomes and first identified POSTN as a significant upregulated gene encoding periostin. This secreted cell adhesion protein is known to be overexpressed in other carcinomas with metastasis- promoting function. We therefore explored the significance of periostin immunoexpression status in a well-defined cohort of NPC patients. Design: Periostin immunohistochemistry was retrospectively performed and analyzed using H-score method for biopsy specimens from 124 NPC patients receiving standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as overexpressed. The results were correlated with the clinicopathological variables, disease-specific survival (DSS), local recurrent-free survival (LRFS) and distant metastasis-free survival (DMFS). Results: Periostin overexpression was significantly associated with N2-3 status (p=0.004) and AJCC stages III-IV (p=0.006) and univariately predictive of adverse outcomes for DSS (p=0.0002), LRFS (p=0.0138) and DMFS (p=0.0028). In multivariate comparisons, periostin overexpression still remained prognostically independent to portend worse DSS (p=0.003, hazard ratio=2.311) and LRFS (p=0.024, hazard ratio=3.187), together with advanced AJCC stages III-IV. Conclusions: Periostin expression is upregulated in a subset of NPCs and its increased immunoexpression significantly correlated with advanced disease and tumor aggressiveness, justifying the potentiality of POSTN as a prognostic biomarker of NPC.