DNA ploidy was investigated in 61 specimens obtained from 25 patients with squamous carcinoma of the oral and maxillofacial region. Biopsy specimens of normal tissue surrounding the tumor were also obtained in six patients. Single-cell suspensions for flow cytometric analysis were prepared. The DNA ploidy and histogram were calculated and compared with the histologic grade, presence of lymph node metastases, and course of the disease. The ploidy of the main stemline was peridiploid in 17 carcinomas, hyperdiploid in three, and aneuploid in five. Histologic grade but not nodal involvement was associated with the ploidy of the main stemline. Of 15 multisampled carcinomas 13 showed constant DNA ploidy and histogram classification. In the other two major changes in DNA ploidy (from peridiploid to hyperdiploid in the first and from peridiploid to aneuploid in the second) were found. Survival information was available for 24 patients. Ploidy values higher or lower than 2.5 c were strongly predictive of both overall (p < 0.001) and relapse-free survival (p < 0.001). The lymph node status proved a powerful prognostic indicator (p = 0.014) but was not related to the relapse-free time of survival. Multiparametric evaluation of survival revealed an independent role of both DNA ploidy and nodal involvement in the prognosis of squamous carcinoma of the oral and maxillofacial region.