The two-dimensional gel electrophoresis (2-DE) approach was used to evaluate the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC) and to detect differentially expressed proteins which could be used as specific and sensitive biomarkers for early diagnosis of the disease. We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with World Health Organization (WHO) type III NPC to 2-DE and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data showed higher expression of ceruloplasmin (CPL) and lower expression of α2-HS glycoprotein (AHS) in the serum high abundance 2-DE protein profiles of NPC patients as compared to that of the normal healthy controls. The ceruloplasmin (CPL) and α2-HS glycoprotein (AHS) spots were identified by mass spectrometric analysis and Mascot database search. In conclusions, this information may help in early diagnosis of nasopharyngeal carcinoma.