Pheochromocytomas and extra-adrenal paragangliomas are tumors of the paraganglia with similar histological characteristics. We examined 12 sporadic pheochromocytomas and 5 extra-adrenal paragangliomas for loss of heterozygosity (LOH) in chromosomes 1p and 3p using a microdissection technique. Chromosomes 1p34-36, 3p21 and the von Hippel-Lindau (VHL) gene locus (3p25) were analyzed. LOH of a selected region on chromosome 1p was detected in 5 of 11 (45%) informative pheochromocytoma cases and in 0 of 5 (0%) informative extra-adrenal paraganglioma cases. LOH of the chromosome 3p25 VHL gene locus was detected in 5 of 9 (45%) informative pheochromocytoma cases and in 0 of 3 (0%) informative extra-adrenal paraganglioma cases. LOH of 3p21 was detected in 2 of 4 (50%) informative extra-adrenal paraganglioma cases. The allelic deletions in chromosomes 1p and 3p appear to be separate events. In conclusion, significant deletions were found at 1p34-36 and 3p25 in sporadic pheochromocytomas but not in extra-adrenal paragangliomas. These findings suggest (1) that multiple genetic factors may be involved in pheochromocytoma tumorigenesis, and (2) extra-adrenal paragangliomas may have a different genetic mechanism of tumorigenesis compared with pheochromocytomas.