Several recent studies have investigated DNA instability in malignancies including deletions and duplications of part of the chromosome using array-based comparative genomic hybridization (CGH) analysis. Using the same approach on oral squamous cell carcinoma (OSCC) tissue samples, we found a frequent deletion at chromosome 3q26.1 in OSCC patients; this polymorphism showed a gene frequency of 0.293-0.368 in healthy volunteers (n=60) and 0.129-0.195 in OSCC patients (n=54). Detailed analysis around the polymorphic region revealed the deletion breakage point. A significant association of gene frequency for the deletion polymorphism between healthy volunteers and patients implicated genetic factors related to this polymorphism in the development of OSCC. Currently, no gene is predicted to lie within the 3,606-kbp region around the polymorphism. Thus, although a single-gene model could not explain the occurrence of OSCC, we believe that examining this polymorphism could be useful in identifying risk factors for OSCC.