Nasopharyngeal carcinoma (NPC) is a malignancy associated with remarkable racial and geographic factors. The development and progression of NPC may involve the accumulation of multiple genetic alterations over a long time. For understanding the putative order of genetic alteration in NPC tumorigenesis, we used evolutionary tree models (branching and distance-based tree models) to analyze comparative genomic hybridization (CGH) data of previously published NPC cases (n = 103). Consistent loss of 3p for both tree models was an important early event in NPC progression. Chromosome 12 gain was another important early event, and may represent a subclass different from 3p- derived subclasses of NPC. The tree models also suggested that at least two subclasses of 3p- derived NPC, one marked by 1q+, 9p-, and 13q- and the other marked by 14q-, 16q-, 9q-, and 1p-.