In a retrospective study, we examined 34 premalignant lesions of the oral cavity by flow cytometer analysis on formalin-fixed, paraffin-embedded tissue submitted to the University of Tennessee, Memphis, Oral Pathology Laboratory. Three categories of oral epithelial dysplasia were represented (eight mild, seven moderate, nine severe), as well as five epithelial hyperplasias without dysplasia and five fibrous nodules as controls. The DNA index and total proliferative index of each case were calculated. The objective of the study was to determine the amount of epithelial dysplasia necessary in oral lesions before DNA aneuploidy or high proliferative index is detectable and thus determine if flow cytometric analysis can be a diagnostic adjunct for oral premalignant lesions. The results showed that some cases in both the control and dysplastic categories exhibited a high total proliferative index (control = 1, no dysplasia = 1, mild dysplasia = 3, moderate dysplasia = 2, severe dysplasia = 2), whereas only the dysplastic lesions had an abnormal DNA index [8 of 24 (33%)]. The results indicate that flow cytometric analysis may have some limited potential as a diagnostic adjunct in oral premalignant lesions.