Although relatively rare, endocrine tumors of the digestive tract and pancreas have been widely investigated and represent a complex tumor entity. The two major categories of well-differentiated and poorly differentiated tumors show important phenotypic and clinical differences. In well-differentiated tumors the multiple endocrine neoplasia syndrome of Type 1 (MEN1) gene is frequently abnormal, though a complex multiple gene involvement is postulated for different tumor types. Poorly differentiated carcinomas show frequent p53 gene hyperexpression/defects, characterizing severe cell abnormality and possibly accounting for the malignancy of such carcinomas.