Gastrointestinal mesenchymal tumors are tumors caused by gene mutations; therefore, gene mutation testing is important to help diagnose some difficult cases, predict the efficacy of molecularly targeted therapies, and guide clinical treatment. It is recommended that genetic analysis should be performed when the following conditions exist: (1) all initially diagnosed recurrent and metastatic GISTs, for which molecular targeted therapy is proposed; (2) after surgery for primary resectable GIST, intermediate one high risk of recurrence, for which imatinib adjuvant therapy is proposed; (3) c-kit or PDGFRA mutation analysis should be performed for difficult cases to clarify the diagnosis of GI; (4) identification of NF1 type GIST, complete or incomplete Carney’S triad, familial GIST, and pediatric GIST; (5) Differentiate between simultaneous and heterochronic multiple primary GIST.