The aim of this article is to provide a short review of the literature concerning the basic principles, usefulness and limitations of ultrasound-guided biopsy of musculoskeletal softtissue tumors, with particular focus on core needle biopsies. Musculoskeletal soft-tissue tumors represent a rare and complex group of heterogeneous lesions. Prompt diagnosis of these uncommon lesions can improve the outcome and increase the patient survival rate. A biopsy examination of soft-tissue tumors with imaging modalities is necessary in all cases of aggressive or undetermined lesions. Although fine needle aspiration can be helpful for the biopsy of certain tumor types, core needle biopsy is a standard procedure in most tertiary sarcoma centers. It has a high diagnostic accuracy, low complication rate and lower price in comparison to open biopsy, and can replace it in the majority of cases of soft-tissue tumor assessment. However, the examining physician has to be familiar with the technique, and the strengths and potential difficulties in performing ultrasound-guided biopsy, as well as possible solutions to obstacles. Several recently developed ultrasound techniques can be helpful and improve the outcome of imaging-guided biopsies of musculoskeletal lesions.