Head and neck cancer is one of the most frequent tumor types and the most common variant is the squamous cell carcinoma of the upper aerodigestive tract (HNSCC). The therapeutic strategies for HNSCC are based on the TNM stage and tumor site. However, tumors showing the same clinical stage and site treated by the same protocols present different recurrence and survival rates. A better knowledge about the biological behavior of HNSCC would guide to a more precise delineation of tumor progression and biological potential of invasion and metastasis. In this context, the identification of molecular markers plays an important role in the determination of the prognosis and follow-up of cancer patients adjusting the treatment to the agressiveness behavior of the tumor. The objective of this study is to determine the hypermethylation profile of promoter regions of tumor supressor genes in HNSCC samples from American and Brazilian patients in order to evaluate the utility of hypermethylation of these genes as molecular markers for HNSCC. Ten genes (P16^INKa, MGMT, DAPK, MINT31, CCNA1, CCND2, TIMP-3, ESR, AIM-1 and DCC) were selected for the hypermethylation analysis in samples of HNSCC from patients treated at Johns Hopkins University and at Hospital do Câncer A.C. Camargo. The hypermethylation profile analysis was performed by quantitative methylation specific PCR, after sodium bissulfite treatment. Regarding the Jonhs Hopkins University patients, hypermethylation of at least one gene was detected in 101 (97,1%) cases and the most frequent methylated genes were DCC (78,8%), DAPK (74,0%), ESR (70,2%) and TIMP-3 (70,2%). All the genes were considered good markers for HNSCC. It was also possible to correlate the hypermethylation profile of some genes to the anatomic site, alcohol and tobacco consumption. Now we are evaluating the hypermethylation profile of HNSCC in 104 samples from Brazilian patients. Supported by FAPESP.