Malignant tumors of the paranasal sinuses constitute less than 1% of all malignancies. Unfortunately, few prognostic factors have been identified regarding the efficacy of interventional therapy. Patients with carcinoma of the maxillary sinus frequently present with an advanced stage of disease and multimodality therapy is often proposed. Although some tumors appear to be more sensitive to preoperative chemotherapy and radiation therapy, a method of predicting and evaluating tumor behavior has not been recognized. Introduced as a means of identifying cell populations with abnormalities in total DNA content, flow-cytometric DNA analysis provides a quick and reliable means of tumor characterization for many malignancies. Although 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 is conflicting and incomplete. To evaluate the role of flow-cytometric DNA analysis in predicting therapeutic alternatives, 22 patients with squamous cell carcinoma of the maxillary sinus were reviewed. Patient outcome and histopathologic grade were retrospectively compared with flow-cytometric evaluations of paraffin-embedded formalin-fixed tumor specimens. Four of sixteen tumors (25%) were found to be aneuploid and were also associated with an increased survival rate (p < 0.01). This initial data emphasizes the possible usefulness of DNA measurement for characterization of squamous cell carcinoma of the maxillary sinus and stresses the need for further evaluation.