Summary:This commentary addresses the nature of interstitial cells of Cajal (which can now be conveniently demonstrated by immunostaining for c-kit) and their possible role in the genesis of various motility disorders of the gastrointestinal tract. The evolution of the concept on the nature of gastrointestinal stromal tumors is discussed, with emphasis on the recent finding of a very high frequency of c-kit immunoreactivity in these tumors, suggesting that they might exhibit differentiation toward interstitial cells of Cajal. The practical immunohistochemical applications of antibodies to c-kit in diagnostic pathology are also discussed.