Exposure of the mucosa of the upper aerodigestive tract to carcinogens can induce genetic changes resulting in various independent clones of neoplastic growth, a concept defined as "field cancerization." The risk of developing multiple tumors in this compartment of the body is well established. We studied 6 distinct tumors of the upper aerodigestive tract of a single patient for loss of heterozygosity (LOH), microsatellite instability (MSI), p53 mutations, and K-ras codon 12 point mutations. We detected a unique pattern of LOH and p53 mutations in all 6 tumors. No tumor showed a K-ras mutation or MSI. The results support the mechanism of "field cancerization" and illustrate the potential power of molecular techniques to elucidate pathogenesis.