DNA gains targeting the 3q chromosome are common in head and neck squamous cell carcinomas, as well as in lung, ovarian, and cervical cancer. Several candidate oncogenes located on 3q were proposed, i.e., PIK3CA, p63, and eIF-5A2. However, none of these genes was found included in a narrow high-level amplification. Recently, microarray-based comparative genomic hybridization (array CGH) was developed for high-resolution screening of deletions and amplifications in tumor genomes. In this study, by microarray-based comparative genomic hybridization, we found a narrow 3q25.3 high-level amplification in a head and neck cancer cell line. We precisely delimited the 3-Mb length-amplified segment by semiquantitative PCR and measured the transcriptional level of every gene (RefSeq full-length mRNA) located inside this segment by cDNA microarray and quantitative reverse transcription-PCR. Four genes were overexpressed in three head and neck cancer cell lines with increased DNA copy number, compared with a control tongue cell line. We extended the transcriptional analysis of these four genes to 20 head and neck squamous cell carcinomas. Only one gene, cyclin L (ania-6a), is commonly overexpressed in primary tumors compared with corresponding normal tissues. This cyclin was previously pinpointed as a candidate for a role in promoting cell cycle entry. Thus, we propose cyclin L as a candidate oncogene in head and neck cancer.