The goals of this study were to evaluate the potential of detecting cryptic amplification and deletion of cancer-related genes using array-based comparative genomic hybridization (CGH), and to identify candidate cancer genes by combined parallel analyses of copy number and gene expression profiles in nasopharyngeal carcinoma (NPC) cell lines. We established global DNA copy number and mRNA expression profiles on human NPC cell lines using a high-density cDNA microarray. The DNA copy number alterations detected by array CGH were compared to the DNA copy number variations identified by metaphase CGH. A cryptic amplification at 3q26 was detected by array CGH, which was not found by metaphase CGH. By amplicon mapping and parallel analyses of DNA copy number and mRNA expression levels, we identified several candidates which could be important mediators in tumor formation or progression. Taken together, the combination of copy number and gene expression profiling using cDNA microarrays provides an improved strategy for gene discovery in human cancer.