Squamous cell carcinoma is the most frequent malignant tumor of the oral cavity. Markers of tumor progression that could help to define diagnosis, plan treatment and implement prognosis have still to be identified. Seven candidate markers for tumor progression were investigated using a loss of heterozygosity (LOH) assay. The sample was made up of 51 squamous cell carcinoma and adjacent normal tissues from the same patients. LOH at one, or more, markers was a relatively frequent event that was observed in 53% of tumors. The number of losses detected in each tumor was significantly associated with tumor severity. Significant association between UICC stage grouping and LOH was found for 3 gene loci: programmed cell death 4 (PDCD4), catenin beta 1 (CTNNB1), and caspase 4 (CASP4). No association between allelic loss and the occurrence of lymph node metastasis was found for any of the seven investigated loci. Overall, LOH contributes to tumor progression of oral SCC. A specific role for PDCD4, CTNNB1, and CASP4 was found.