To assess the difference in genetic aberration patterns among the invasive tumor front (ITF), center/superficiality and the stroma adjacent to oral squamous cell carcinoma (OSCC), we studied loss of heterozygosity (LOH) and microsatellite instability (MI) at chromosome 9p21 and 17p13 on the three regions by combining laser capture microdissection (LCM) and PCR. We studied 20 OSCC patients with TP53 on chromosome 17p13 and RPS6 on chromosome 9p21. Genomic DNA samples from the ITF, center/superficial and stromal cells adjacent to the tumor were prepared from cryosections using laser-assistant microdissection, then LOH and MI were determined. Cells at the ITF, center/superficiality and stroma showed a high frequency of LOH and MI on chromosomes 17p13 (TP53) and 9p21 (RPS6). Comparison of the patterns of allelic loss and MI encountered at the ITF, center/superficial and stromal cells revealed no concordance. The frequency of RPS6 and TP53 aberration at the epithelial compartment (both ITF and center, 64.7%, 11/17; 70.6%, 12/17) was statistically higher than the stroma (23.5%, 4/17; 43.8%, 7/16) (p<0.05). Furthermore, for the epithelial compartment, the aberrations proportions of TP53 rose from 60.0% (9/15) to 64.7% (11/17) between the center/superficial part and ITF. Also the rate of RPS6 increased from 29.4% (5/17) to 58.8% (10/17) between the center/superficial parts and ITF. The overall frequency of the two markers was statistically higher at the ITF (20/32) than the center/superficial part (15/34) (p<0.05). The current study revealed that intratumor genetic heterogeneity exists in the different histological areas of OSCCs and some particular tumor cell genotypes have correlation with histological patterns.