High-resolution array-CGH was performed to identify differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2-q29, 12p13.2-p13.33, and 19p13.3, as well as losses at 3p26.2-p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2-q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at 3q26.2-q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Overall design: Array-CGH was performed to compare the different patterns of genetic alterations. DNA from NSCLC patients (n=36) and human reference DNA (Promega) were differentially labeled and cohybridized on the array. The Fisher exact test utilized two categories, normal and abnormal (loss and gain), with the null hypothesis that the relative proportions of each of the two imbalance categories would be expected to be the same in the groups. The counts of abnormal versus normal were summarized by subtype of NSCLC for each BAC, providing 2x2 tables for analysis. A multiple testing correction (Benjamini-Hochberg false discovery rate (FDR)) was applied to correct for the high number of false positive calls.