Nuclear DNA content has been implicated as a prognostic factor in an increasing number of tumor types. Current data on the role of DNA content in head and neck carcinoma are conflicting and incomplete. To evaluate the role of DNA content in predicting radioresistance, 29 patients with T1N0M0 squamous cell carcinoma of the glottic larynx who had undergone uniform curative radiotherapy and whose clinical outcome was known had flow cytometric analysis for DNA content performed on their tumors with paraffin-embedded archival tissues. Five aneuploid lesions and 24 diploid lesions were identified. All aneuploid lesions occurred in radioresistant tumors. The probability of an aneuploid tumor failing radiotherapy was highly significant at p = .016. No DNA discordance was found in a sampling of half of the radioresistant lesions' pretreatment and recurrent specimens, for a 100% predictive value of moderate statistical power. On the basis of these findings, patients with aneuploid T1 glottic lesions should be referred for primary surgical therapy.