The DNA contents in 56 laryngeal glottic biopsy specimens with a spectrum of squamous intraepithelial neoplastic (SIN) changes were evaluated by image analysis. A combination of DNA histogram features were used to define abnormal DNA-containing cell populations that were interpreted as representing intraepithelial neoplastic transformation. Eighteen biopsy specimens were classified as dysplasia/keratosis and graded SIN I, six (33%) of which were aneuploid. Eighteen (78%) of 23 biopsy specimens graded SIN II were aneuploid, and all 15 biopsy specimens graded SIN III had abnormal quantities of nuclear DNA. Twelve biopsy specimens (six of SIN II grade and six of SIN III grade) were considered to represent keratinizing forms of dysplasia, and all 12 (100%) were found to contain increased (aneuploid) quantities of DNA. We conclude that the proposed SIN-grading scheme for laryngeal epithelial abnormalities exhibits strong correlations with nuclear DNA content. In addition, aneuploidy was observed in all SIN II- and SIN III-graded biopsy specimens with prominent keratinization.