Insulinomas are the most common functioning pancreatic endocrine tumors, and the previous studies showed that the chromosomal aberrations of Chr.9q, 11q, and 22q were associated with the development and progression of insulinoma. To analyze the genetic alterations in sporadic insulinoma, we tested 23 tumor samples using multiplex ligation-dependent probe amplification. The results showed that 20 (87%) of the 23 patients had lost CDH1, a tumor suppressor gene. Immunofluorescence analysis of the E-cadherin and beta-catenin proteins further confirmed the impaired expression of E-cadherin and the translocation of beta-catenin in sporadic insulinomas. It was found that the cytoplasmic accumulation of beta-catenin coincided with the decrease or loss of E-cadherin synthesis during the tumorigenesis of sporadic insulinomas. Our study suggests that the inactivation of CDH1 is an important and early event in the development of these tumor types.