Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected in one patient. Of the 37 patients, 29 were informative at APC or MCC or both; LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play a role in the pathogenesis of human oral SCCs in Taiwan.