Abstract
Gastrointestinal stromal tumors (GISTs) are rare entities, which, however, represent the most common mesenchymal tumor of the gastrointestinal tract. The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor. This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors (TKIs), which terrifically revolutionized the prognosis of GIST patients. Currently, it is well established that tumor mutational status is the main player in clinical outcome; however, with the research advances, it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes. For this reason, in the era of tailored/personalized medicine, each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.