Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently have deletions of chromosome 1, suggesting that inactivation of a tumor suppressor gene from chromosome 1 is important in their tumorigenesis. We hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied. Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8) than tumors without metastases (3 of 21) (P = 0.004). Tumors in patients with lymph node involvement and patients with multiple endocrine neoplasia type 1 did not demonstrate LOH for chromosome 1 markers. These data suggest that loss of chromosome 1 is associated specifically with the development of hepatic metastases in patients with sporadic pancreatic endocrine tumors.