Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin-embedded archival tumor specimen blocks were performed by flow cytometry on extracted nuclei from 75 pheochromocytomas. Clinical details, specifically including histologic findings, biochemical studies, and ultimate fate, were investigated. Preparation of paraffin-embedded tissue specimens was carried out by the technique of Hedley et al. and stained with propidium iodide according to the method of Vindeløv et al. Twenty-three tumors showed a normal DNA histogram, 31 showed significant increase in the 4C (DNA tetraploid) peak, and 21 exhibited a DNA aneuploid peak. To define a subset of patients who had either died as a result of pheochromocytoma or had been followed for a minimum of 10 years, 13 patients were excluded. Of the remaining 62 patients, all of the 18 patients with a normal DNA histogram followed a benign clinical course, including normal fractionated urinary catecholamines. However, eight (31%) of the 26 patients classified DNA tetraploid/polyploid and seven (39%) of the 18 patients exhibiting a DNA aneuploid peak had evidence of malignancy; these two groups had significantly more malignant tumors (p less than 0.05 and p less than 0.02, respectively) than the normal DNA group. Flow cytometric DNA ploidy measurements of isolated nuclei seem to provide useful prognostic information for patients with pheochromocytoma.