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Uterine sarcomas are rare, aggressive tumors with poor prognosis that can be further negatively affected by inadequate surgical approaches such as morcellation. There are no clinical and radiologic criteria for differentiating leiomyoma from malignant uterine tumors. However, some ultrasonography and magnetic resonance imaging findings may be informative. We present a technique of ultrasound-guided trans-uterine cavity (UG-TUC) core needle biopsy for uterine lesions. As the procedure is an in-organ biopsy, there is no risk of needle canal contamination. The technique also enables the biopsy of lesions inaccessible by the transvaginal tru-cut biopsy. The core needle of the automatic biopsy system is inserted via the cervical canal into the uterine cavity and is directed and activated at the myometrial lesion under ultrasound control. The standard local treatment of localized uterine sarcomas is en bloc total hysterectomy; for fibroids, there are multiple options including conservative management or tumorectomy and tumor morcellation using minimally invasive techniques. Fragmentation of the sarcoma significantly worsens oncologic outcomes and should therefore be avoided. The UG-TUC core needle biopsy of uterine lesions can complement imaging to obtain sufficient material for histologic and molecular analyses of suspected or undetermined lesions, thus facilitating treatment planning and decreasing the risk of unsuspected sarcomas.