To examine whether genetic factors influence the prognosis of cancer patients, several polymorphic markers were used to determine the allelic loss of certain areas of the genome. Two polymorphic markers, IFNA and D9S171 were used to study the loss of heterozygosity (LOH) of chromosome 9p21 in 75 head and neck squamous cell carcinomas. LOH was detected in 14 out of 64(22%) DNA samples obtained from cancer specimens when at least one marker was used. The frequency of LOH was not correlated with the localization of the tumor, clinical stage of the patient, tumor size and lymph node involvement. However, the frequency of LOH was significantly higher in the recurrent tumors than in the non-recurrent tumors, suggesting that the allelic loss at 9p21 can be correlated with the short term prognosis of the patients. LOH was identified in only three out of 19(16%) samples when D7S522 was used as a marker. However, all of these three cases were recurrent, and two of the three showed the allelic loss at 9p21 at the same time. These results indicate that LOH of 9p21 and/or 7q31 is a novel prognostic factor independent of other clinical factors for head and neck squamous cell carcinoma. Replication error (RER) was observed in 4 cancers, implicating genetic instability in the carcinogenesis of a subset of head and neck squamous cell carcinoma.