Hyaline globules (HGs; thanatosomes) are well-defined morphologic and functional entities representing a degenerative phenomenon common to all cell types. We present the first quantitative and qualitative study of HGs in normal and pathologic gastrointestinal (GI) epithelium from a series of 2,230 biopsies. HGs were very rarely found in normal epithelium (1.1%), but their number increased significantly in specimens with ischemic injury (47%) and benign regenerative proliferation (70%). Their incidence in adenomatous polyps and adenocarcinomas was about 11% to 27%. Of the HGs, 2.9% contained nuclear fragments. Our results entirely support the unifying morphogenetic concept for HGs. The role of 2 obligatory morphogenetic factors for the generation of thanatosomes (propensity to apoptosis and heterophagy/autophagy) is confirmed. The nature of the third factor, ischemic conditions, is specified. Although a nonspecific microscopic phenomenon, HGs in the GI tract represented a relatively constant and useful histologic marker of enhanced cell turnover and ischemic injury.