Abnormal DNA content (aneuploidy) has been associated with malignant and premalignant epithelial lesions. The presence of aneuploidy in tumours at an early stage and in dysplastic lesions suggests that analysis of DNA content may be a useful marker for determination of prognosis in these lesions. The aim of this study was to use DNA image cytometry to evaluate aneuploidy in oral dysplastic lesions and to determine whether aneuploidy is associated with malignant progression. Forty-two lesions of oral epithelial dysplasias (OED) that had progressed to oral squamous cell carcinoma (OSCC) and 44 lesions that did not progress were analysed for DNA ploidy using image cytometry of nuclear monolayers prepared from paraffin-embedded tissue. Forty-two OSCC that had arisen from the OED cases and five samples of normal oral mucosa samples (NOM) were also examined. Aneuploidy was found in 14/42 (33.3%) of the OED that progressed, but in only 5/44 (11.3%) of OED that did not progress (p=0.01). A total of 19 OED were aneuploid of which 74% showed malignant progression compared to only 42% of the diploid lesions. The sensitivity and specificity of DNA image cytometry to detect cases with high risk of malignant progression was 0.33 and 0.88, respectively. The PPV and NPV were 0.74 and 0.58. We conclude that aneuploid oral dysplastic lesions have a high risk of malignant progression and that DNA image cytometry might help to identify those lesions most at risk.