Adenocarcinoma of the lung is now the most common histologic subtype of non-small-cell lung cancer (NSCLC) worldwide. In Chinese populations, the incidence of lung adenocarcinoma is amongst the highest worldwide and its development in non-smoking females is particularly striking. Information on the associated underlying genetic changes has been, however, minimal to date. The present study represents the first systematic analysis on the overall genetic changes in lung adenocarcinoma of Chinese female non-smokers. We undertook a genome-wide investigation into the abnormalities in lung adenocarcinomas of 18 life-long non-smoking Chinese females using the technique of comparative genomic hybridization (CGH). With a view to isolating the relative roles of gender, ethnicity and tobacco consumption, we recruited control groups of 10 Caucasian female non-smokers and 22 male Chinese smokers. Although gains on 1q, 5p, 7p and 8q, and regional losses on 8p, 17p, 13q and 18q were commonly seen, there were no significant differences between the Caucasian and Chinese non-smoking women. The observation suggests that lung adenocarcinomas, regardless of ethnic origin, adopt similar pathologic pathways during the accumulation of genetic events. Besides, genomic imbalances, particularly gains per tumor, were significantly more common among the tobacco-related tumors (P=0.006). In particular, regional over-representations of 13q21-q34 (P=0.044), 17q25 (P=0.015), 19q13.1 (P=0.044) and 22q (P=0.044) may have implications for the pathologic pathways associated with the tobacco-related lung adenocarcinoma.