Genome-wide microarray-based comparative genomic hybridization (array CGH) was used to identify common chromosomal alterations involved in cervical carcinogenesis as a first step towards the discovery of novel biomarkers. The genomic profiles of nine squamous cell carcinomas (SCCs) and seven adenocarcinomas (AdCAs), as well as four human papillomavirus (HPV)-immortalized keratinocyte cell lines, were assessed. On a genome-wide scale, SCCs showed significantly more gains than AdCAs. More specifically, there was a striking and highly significant difference between the two histological types for gain at 3q12.1–28, which was predominantly observed in SCC. Other frequent alterations included gains of 1q21.1–31.1 and 20q11.21–13.33, and losses of 11q22.3–25 and 13q14.3–21.33. Subsequent FISH analysis for hTR, located at 3q26, confirmed the presence of 3q gain in SCCs and HPV-immortalized cell lines. Fine mapping of chromosome 20q using multiplex ligation-dependent probe amplification (MLPA) showed copy number increases for a number of genes located at 20q11–q12, including DNMT3B and TOP1. For DNMT3B, this correlated with elevated mRNA expression in 79% of cases. In conclusion, the assessment of frequent genomic alterations resulted in the identification of potential novel biomarkers, which may ultimately enable a better risk stratification of high-risk (hr)-HPV-positive women. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.