Cytologic smears of squamous cell carcinomas (UICC T2 through T4) from the mucosa of the upper aerodigestive tract without cervical lymph node metastases (n = 10) and with metastases (n = 20) were examined. Subsequently, the cytologic smears of the metastases (n = 20) obtained by fine-needle aspiration or following neck dissection were evaluated morphologically. Each specimen was then stained with Papanicolaou and Feulgen techniques, and quantitative DNA measurements were performed with an image analysis system. Morphologically, the primary tumors with metastases revealed an increased mean nuclear perimeter and mean nuclear area compared with tumors unassociated with metastases. On quantitative DNA measurements, the tumors with metastases had an increased DNA content, a higher 2c deviation index, and a higher DNA malignancy grade and increased number of aneuploid cells. The specimens obtained from the metastatic nodes yielded the highest values for mean DNA content, 2c deviation index, aneuploidy, and malignancy grade. The stem lines of metastasis were always nondiploid. These data indicate a positive correlation between aneuploid tumor cell clones in primary cancer and the manifestation of lymph node metastases.