A microsatellite assay was used to screen 31 potentially malignant oral lesions presenting as leukoplakia and erythroplakia, with histological evidence of dysplasia, for genetic abnormalities at loci which frequently show allelic imbalance when oral squamous cell carcinomas (SCC) are examined. The microsatellite and restriction fragment length polymorphism (RFLP) markers selected were at 3p21, 8p21-23, 9p21 and included sequences within the Rb (13q14.2), p53 (17p13.1) and DCC (18q21.1) tumour suppressor genes. 8 patients subsequently developed an invasive tumour at the same site, or within 2 cm of the premalignant lesion. A further 8 patients developed SCC at a distant site. Seventy-seven per cent (24/31) of these potentially malignant lesions showed allelic imbalance (AI) and 55% (17/31) of cases showed microsatellite instability (msi). The probability of developing SCC was much greater for patients with lesions showing AI at two or more relevant loci (P = 0.008 by the logrank test) than the group with AI at fewer loci. The estimated probability of development of SCC in this group by 5 years was 73% (95% Cl: 50-92%). This suggests that determining the number of genetic abnormalities in a potentially malignant lesion can help identify patients with true precancers who should be followed closely to ensure that they receive chemoprevention and appropriate advice to limit risk factors, and to allow the early detection of invasive lesions.