BACKGROUND: The authors evaluated the effectiveness of the oral brush biopsy technique as a diagnostic tool in detecting dysplastic oral lesions. METHODS: In this cross-sectional study, pathologic reports (n=152) from the scalpel biopsies (tissue samples) in patients who previously tested either "positive" (n=3) or "atypical" (n=149) for dysplasia by brush biopsy (OralCDX) were evaluated. Information on the age and sex of the patient, the site of the lesion, the brush biopsy results, and the histopathologic diagnosis of the scalpel biopsy was collected. The positive predictive values (PPVs) for "abnormal," "atypical," and "positive" brush biopsies were determined. RESULTS: Overall, the PPV of an abnormal brush biopsy was only 7.9% (95% confidence interval [CI], 4.2%-13.4%), and the PPV of an "atypical" brush biopsy was 7.4% (95% CI, 3.7%-12.8%). Of the 3 positive brush biopsies, only 1 was identified as dysplastic. The proportion of false-positive biopsy results was as high as 92.1% (95% CI, 86.6%-95.9%). CONCLUSIONS: The OralCDx technique overestimated dysplastic lesions and produced a high number of false-positive results. Cancer 2009;115:1036-40. (c) 2009 American Cancer Society.