Thirty-six patients underwent biopsy of clinically suspicious lesions of the mucosa of the upper aerodigestive tract. The biopsy material was evaluated histologically and cytologic smears out of the same lesion underwent quantitative DNA analysis using a numerical index derived from the single cell DNA content. In 30 patients, histologically diagnosed squamous cell cancer was confirmed by DNA analysis with the malignancy grade correlating with the morphologic differentiation of the tumor. Six lesions were histologically benign: i.e. dysplasia (n = 3), hyperplasia (n = 2) and chronic inflammation (n = 1). DNA analysis confirmed the benign nature in 4 cases, but in 2 cases of dysplasia, a diagnosis of malignancy was made. From these results, there appears to be an excellent correlation between DNA analysis and the histologic diagnosis of malignancy. It remains to be proven if this technique of DNA analysis will prove to be a more accurate determinant of malignant potential in premalignant conditions and a method to determine aggressiveness of behavior. An added advantage is that this technique can be performed on cytologic smears, without the need for incisional biopsy.