Introduction: The gastrointestinal stromal tumors (GIST) are dominated by KIT and PDGFRA mutation. The immunohistochemical detection of CD117, a protein express by KIT gene, is essential for the diagnosis and those that are negative always represented a diagnostic challenge Case reports: In this article we present a series of 4 cases of CD117 negative GIST tumors, diagnosed and surgically resected in Fundeni Clinical Institute and an overview of the histogenesis, diagnostic problems and management of c-kit negative GIST. All patients were males and the tumors were located in the stomach and small bowel. Conclusion: It is important for the pathologists to beware of the fact that a CD117 negative in the context of a typical morphological appearance does not exclude a GIST tumor and also the oncologist must be aware not to exclude the therapy with imatinib based on the negativity of CD117.
