Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in the carcinogenesis of many cancers, including squamous cell carcinoma of head and neck (SCCHN). However, microsatellite alterations have not been documented in SCCHN from Chinese patients. We investigated the frequency and clinical significance of LOH and MSI in 30 SCCHN from Hong Kong Chinese using polymerase chain reaction on 17 microsatellite markers on chromosomes 3p, 4q, 7q, 9p, 17p and 18q. LOH was present in nine tumours (30%) and MSI in four (13%). The incidence of LOH (7/13; 53.8%) in hypopharyngeal-laryngeal cancers was significantly higher than that (2/17; 11.8%) in the oral cancers (P=0.020). LOH was more often detected at the loci on chromosomes 7 and 9. Patients with tumours having LOH had slightly poorer outcome compared with those without, although the differences did not reach statistical significance. Our data show that the incidence of microsatellite alterations in SCCHN from Hong Kong Chinese is low. However, LOH may be one of the genetic mechanisms in the carcinogenesis of a subset of SCCHN (hypopharyngeal-laryngeal cancers).