The interstitial cell of Cajal, abbreviated ICC, is a specific cell type with a characteristic distribution in the smooth muscle wall throughout the alimentary tract in humans and laboratory mammals. The number of publications relating to ICC is rapidly increasing and demonstrate a rich variation in the structure and organization of these cells. This variation is species-, region-, and location-dependent. We have chosen to define a "reference ICC," basically the ICC in the murine small intestine, as a platform for discussion of variability. The growing field of ICC markers for light and electron microscopy is reviewed. Although there is a rapidly increasing number of approaches applicable to bright field and fluorescence microscopy, the location of markers by electron microscopy still suffers from inadequate preservation of ultrastructural detail. Finally, we summarize evidence related to ICC ultrastructure under conditions differing from those of the normal, adult individual (during differentiation, in pathological conditions, transplants, mutants, and in cell culture). Copyright 1999 Wiley-Liss, Inc.