Nuclear DNA content and cell kinetics were studied in 40 squamous cell carcinomas of the oral cavity by flow cytometry to evaluate the diagnostic significance of the method in predicting lymph node metastasis. The presence of lymph node metastasis was confirmed histologically in 20 carcinomas. The incidence of metastasis was 36% in group A (22 carcinomas of the tongue and floor of the mouth) and 67% in group B (18 carcinomas of the alveolus and gingiva). On flow cytometric analysis, DNA aneuploidy was observed in 23 tumors (58%). The incidence of lymph node metastasis in the aneuploid tumors was 70%, which was significantly higher than the 24% for the diploid tumors. This also was the case for both of the subgroups. The incidence of aneuploidy and the DNA index for tumors with metastasis were 80% and 1.58, respectively. These values were significantly higher than the 35% and 1.16 for tumors without metastasis, but there were no significant differences in the S phase and G2M phase fractions between the tumors with and without metastasis. The incidence of aneuploidy in tumors with metastasis was also higher in group A (75% versus 36%) and group B (83% versus 33%). In terms of histologic differentiation, the incidence of metastasis and aneuploidy increased as the degree of differentiation decreased. Similar relationships were found between the histologic grade of malignancy and the incidence of metastasis and aneuploidy. The results indicate that nuclear DNA content analysis by flow cytometry is useful as a supplement to clinical and histologic evaluation in predicting the tendency of squamous cell carcinomas of the oral cavity to metastasize to regional lymph nodes.