Pancreatic endocrine tumors (PETs) may be sporadic or inherited in the multiple endocrine neoplasia type 1 (MEN-1) syndrome. The inherited form is caused by mutations of the MEN-1 gene, which functions as a tumor suppressor gene and maps to chromosome 11q13. These tumors tend to have a better prognosis than their sporadic counterparts, which often have mutations of the MEN-1 gene. Previous molecular analyses of sporadic PETs suggest a high frequency of loss of heterozygosity (LOH) at chromosome 1 as well as mutation of MEN-1. In this study we correlate abnormalities of MEN-1 and chromosome 1 LOH with the biological behavior of sporadic PETs. Loss of heterozygosity for markers at chromosome 11q13 and mutation of MEN-1 were equally frequent in tumors with or without liver metastases. Mutation of MEN-1 is more frequent in gastrinomas than in non-gastrinomas. Loss of heterozygosity for markers on chromosome 1 is more frequent in PETs with liver metastases. These results suggest a molecular tumor model in which there is a dichotomy in the development of benign and malignant PETs.