Nasopharyngeal carcinoma (NPC) is a common cancer among southern Chinese. The profile of gene expression in NPC cells is largely unknown. In this study, we have examined differential gene expression in non-malignant and malignant nasopharyngeal epithelial (NPE) cells using a cDNA array hybridization method. A total of 42 genes were identified to be expressed in either non-malignant and malignant NPE cells or both. Thirteen of these genes were overexpressed in malignant NPE cells. These includes nuclear factor (NF90), FOS-related antigen 1 (FRA-1), cytoplasmic dynein light chain (HDLC1), replication factor C (RFC1), nucleoside diphosphate kinase B, UV excision repair protein (RAD23A), insulin-like growth factor receptor II, transcription initiation factor TFIID subunit (TAFII31), growth factor receptor-bound protein 2 (GRB2), UV excision repair protein (RAD23B), glutathione peroxidase, Y box binding protein 1 and heat shock protein 86. In contrast, expression of nine genes was suppressed in malignant NPE cells. These includes calgranulin A, calgranulin B, neutrophil activating protein (ENA-78), heat shock protein 27, integrin beta-1, integrin beta-4, cyclin-dependent kinase inhibitor 1A (p21), interleukin-8 and tyrosine protein kinase receptor (RET). Differential expression of calgranulin A, calgraunlin B, ENA-78, FRA-1 and NF90 in non-malignant and malignant nasopharyngeal epithelial cells was confirmed by RT-PCR analysis.