The detection in tumors of genomic regions with a high frequency of loss of heterozygosity has led to the localization and subsequent cloning of a number of tumour suppressor genes. To identify such regions involved in the development of squamous carcinoma of the head and neck we have analyzed 28 paired normal and tumor DNA samples. Using the polymerase chain reaction to amplify 50 simple sequence repeats or microsatellite markers we have studied all 22 q limbs and 17 of the p limbs in 21 patients. In informative cases we observed a high incidence of loss of heterozygosity at five specific chromosomal regions: 3p (44%); 5q (43%); 9q (35%); 11q (45%); and 17p (31%). In addition, further analysis of tumors showing loss of heterozygosity at 5q suggests that a gene at or near the APC locus is involved in squamous carcinoma of the head and neck.