KIT, a receptor protein tyrosine kinase (RTK), is localized in the plasma membrane and binds stem cell factor. A cancer-causing permanently active mutant of KIT (KITmut) accumulates aberrantly in intracellular compartments. Oncogenic RTK mutants other than KITmut also exhibit characteristic organelle localization, unlike their wild-type counterparts. However, the precise subcellular localization of RTKmut and its biological significance in oncogenic signaling remain unclear. Recent studies have shown that in gastrointestinal stromal tumors (GISTs), KITmut is inappropriately retained in the Golgi/trans-Golgi network (TGN) area in a manner dependent on its tyrosine kinase activity. It is trapped in the biosynthetic secretory pathway in which normal RTK trafficking occurs. Importantly, KITmut is activated and exerts oncogenic signaling predominantly in the Golgi/TGN of GIST cells. Recently, key players in the Golgi retention of KITmut have been reported, but they are unlikely to be involved in the intracellular retention of other RTKs, suggesting that the retention of individual RTKs is regulated by different molecular mechanisms. Here, we review the present knowledge on KIT retention in the Golgi/TGN region in GISTs, molecular mechanisms underlying this retention, and the aberrant localization of other RTK mutants. We also discuss strategies for the medical development of RTK inhibition by blocking intracellular trafficking.