Soft-tissue tumors are not very common, but their diagnosis can be very difficult. In the final analysis, their diagnosis requires a biopsy, which must furnish a sufficient amount of material to allow a reliable histological diagnosis. The authors evaluated the diagnostic efficacy of ultrasound-guided needle biopsy in the diagnosis of soft-tissue tumors of the musculoskeletal system. The aim of the study was to optimize the biopsy procedure, with particular emphasis on the choice of the biopsy needle (large-gauge manual versus semiautomatic) based on the characteristics of the neoplastic mass (consistency, depth, size, location). The results of the study showed that appropriate needle selection significantly reduced the frequency of biopsies that were insufficient for histological diagnosis. The method proved to be highly reliable for diagnosis of soft-tissue tumors but strongly related to the proper selection of the needle to be used.