AIM To evaluate endoscopic ultrasound(EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors(GIST) to personalize the management of patients.METHODS All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase(2006-2011), routine fine-needle-aspiration(EUS-FNA) was performed.In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling(EUS-FNB) for all lesions. c-KIT-and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha(PDGFRA) genes. RESULTS In all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA(98% vs 58%, P < 0.001) and was more adequate for Ki-67-indexing(Ki-67EUS)(92% vs 40%, P < 0.001). Sequencing of EUS-biopsies was successful in 43/44(98%) patients, and the mutation profiles(KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-na?ve patients, the Ki-67_(EUS) was comparable with the Ki-67-index in the corresponding surgical specimens(Ki-67_(SURG))(2.7% vs 2.9%, P = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67 EUS was higher than the Ki-67_(SURG)(2.5% vs 0.2%, P = 0.005), with a significant reduction in the Ki-67-index of-91.5%(95%CI:-82.4 to-96.0, P = 0.005). CONCLUSION EUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy. AIM To evaluate endoscopic ultrasound (EUS) -guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients. METHODS All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed.In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS -FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions. C-KIT-and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki- sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha (PDGFRA) genes. RESULTS In all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared to head-to-head with EUS-FNA (98% vs 58%, P <0.001) and was more adequate for Ki-67-indexing The sequencing profiles of EUS-biopsies were successful in 43/44 (98%) patients, and the mutation profiles (KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding The Ki-67_ (EUS) was comparable with the Ki-67-index in the corresponding surgical specimens (Ki-67_ (SURG)) (2.7% vs 2.9%, P = 0.68 In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67 EUS was higher than the Ki-67_ (SURG) (2.5% vs 0.2%, P = 0.005) 67-index of-91.5% (95% CI: -82.4 to -96.0, P = 0.005) CONCLUSION EUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.