Although considerable knowledge exists on the tumor biology of lung cancer, there is still a need to assess molecular events for the clinical management of the disease. We studied the pattern of chromosomal imbalances in 45 non-small cell lung carcinomas (NSCLC) by comparative genomic hybridization (CGH) and correlated the results with clinicopathological features including immunohistochemical (IHC) expression of the epidermal growth factor receptor (EGFR). Twenty-one tumors were squamous cell carcinomas (SCC) and 24 non-squamous cell lung carcinomas (NSCC) comprising 9 adenocarcinomas (ADC), 9 large cell carcinomas (LCC), 4 sarcomatoid carcinomas and 2 adenosquamous carcinomas. The mean number of individual imbalances was 7.1 for SCC (mean gains, 3.8; mean losses, 3.4) and 6.4 for NSCC (mean gains, 4.5; mean losses, 1.9). Several individual imbalances correlated significantly with increasing number of imbalances, that were +1q, −3p, +3q, −5q, −8p, +8q, +7p, +12p, and +14q. Altogether, the most frequent imbalances were +3q (49%), +5p (49%), −5q (36%), +8q (29%), −8p (24%), −3p (22%), +7p (22%), +12p (22%), +14q (20%), +18p (20%), +1q (18%), and +7q (18%). Among these, +3q and +18p correlated significantly with SCC, and +5p and +14q with NSCC. Remarkably, overlapping imbalances included +3q26, +7p11 in SCC and +1q21, +3q24, +12p11, and +14q12 in NSCC. EGFR expression was higher in SCC than in NSCC and correlated with +3q in the entire series. In addition, +12p correlated significantly with disease progress with the exception of nodal involvement in NSCC as well as with disease progress, regardless of nodal involvement, in the entire series. In conclusion, the present study contributes to the molecular biological characterization of NSCLC histological subtypes and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment.