Pathogenesis of nasopharyngeal carcinoma (NPC) is a multistep and multipathway process that cannot be fully explained by a fixed linear progression model. We used distance-based and branching-tree methods to construct more general tree-like models for NPC carcinogenesis from 170 comparative genomic hybridization (CGH) samples previously published in five smaller studies. Imbalances were classified into “overlap regions,” each containing the most commonly gained or lost band on each chromosome arm as well as adjacent bands that were gained or lost almost as often. The chromosome abnormalities associated with NPC were −3p26–13 (48.9%), −11q22–25 (38.1%), −16q12–24 (38.1%), −14q24–32 (32.4%), −13q21–32 (22.3%), −9p23–21(21.6%), +12p12 (46%), +12q13–15 (43.9%), +1q22–32 (33.1%), +3q13.1–26.2 (30.2%), and +8q22.1–24.2 (27.3%). NPC can be classified into two groups, one marked by +12p12 and +8q22.1–24.2 and the other by −3p26–13, −11q22–25, −14q24–32, and +1q22–32. The tree models predicted −3p26–13 and +12p12 as early events and +8q22.1–24.2 as a late event. The predictions for −3p26–13 and +8q22.1–24.2 were consistent with previous studies. The prediction for +12p12 is being reported for the first time. Many known NPC-related genes on chromosomal regions of these tree models are discussed, some of which may merit additional study. The potential applications of tree models are also discussed. © 2004 Wiley-Liss, Inc.