We evaluated the DNA content of 43 adrenocortical neoplasms by flow cytometry and related it to histopathologic criteria of malignancy and survival. Tumor tissue was selected from paraffin blocks and processed by a modification of the Hedley technique. The tumors were classified as adenomas and carcinomas by the criteria of Weiss. Aneuploid stem-lines were identified in nine of 13 (69%) of the carcinomas and in six of 30 (20%) of the adenomas. Five of the six patients with aneuploid adenomas are alive and well (mean follow-up, 59 months); the sixth was lost to follow-up. Although there was a significant correlation between ploidy and histologic diagnosis (p = 0.041), the sensitivity and specificity of aneuploidy for predicting clinical outcome were only 56% and 65%, respectively. In addition, there was no significant difference in survival between patients with diploid versus aneuploid tumors, despite a highly statistically significant difference in survival between patients with a histologic diagnosis of adenoma versus carcinoma (p = 0.00080). We found correlations between ploidy and tumor size, mitotic rate, and nuclear grade (p = 0.0033, p = 0.0017, and p = 0.018, respectively). There was also a significant correlation between the proliferation fraction of a tumor and its nuclear grade (p = .0093), but not its mitotic count or clinical outcome. Because both adrenal adenomas and carcinomas may contain abnormal DNA stem-lines, ploidy alone is not a reliable discriminator in individual cases.