No single biomarker can predict the risk for malignant transformation of precancerous lesions of the head and neck. Micronucleus frequency, nuclear p53 accumulation and mitotic index were determined in proliferating basal cells using paraffin-embedded specimens from normal, dysplastic and malignant tissues. p53 accumulation was detected by immunohistochemistry using pAb 1081 and pAb 240 antibodies. Micronuclei were scored in the same cell population and classified for the presence/ absence of p53 accumulation in the main nucleus. Fifty-three carcinomas and 15 precancerous lesions were studied. Both micronuclei and p53 accumulation were found in precancerous lesions, suggesting that they are early events in head and neck squamous cell carcinoma progression. The two biomarkers were not related to each other: indeed, micronucleus frequency was higher in p53-negative than in p53-positive cells. Three patients with precancerous lesions later developed carcinomas; all three cases showed high frequencies of both micronuclei and cells accumulating p53 protein.