Cytogenetic findings were identified in 5 adrenal pheochromocytomas (PCC), including two clinically malignant tumors. The 3 PCC with benign clinical behavior, including one associated with von Hippel-Lindau syndrome, displayed no clonal chromosomal aberrations. In contrast, both clinically malignant PCC were characterized by hypotriploid chromosome numbers and multiple numerical and structural changes involving various chromosomes. Overall, losses were observed more frequently than gains. Aberrations common to both malignant tumors included losses of chromosomes 4, 11p, 13q, 15q, 16p, 17p, and 18, and partial gains of chromosome 7. The present results indicate that the malignant phenotype in PCC is associated with considerable genetic instability, leading to highly aneuploid and aberrant karyotypes.