The most important indicator of ploidy and cell cycle stage in ortho- and pathologic tissues is the nuclear DNA content. To study this parameter of malignancy in squamous carcinomas of the oral, pharyngeal, or laryngeal mucosa we analyzed DNA histograms by aid of flow cytophotometry after using pepsin digestion of tumor specimens for cell dispersal and fluorochromation with combined ethidium bromide and mithramycin. In 30 of 36 tumor tissue specimens aneuploid states of nuclear DNA content (83%) were recognized, in some cases only by comparing tumor cells with admixed diploid human reference cells. All but two tumors (with hypodiploid DNA pattern) exhibited hyperdiploid stem line abnormalities, one specimen even exhibited them with triclonal DNA distribution pattern. The degree of ploidy (DNA index), defined as the ratio of peak modal channel number for the G1/0 proportion of tumor cells to that of normal cells, ranged from 0.59 to 3.24 (mean 1.58). Cell cycle analysis of untreated squamous carcinomas, calculated by the relative DNA distribution pattern in histograms, also offered a considerable variation in proliferative activity.