Introduction: Percutaneous ultrasound-guided core needle biopsy is a well-established method in the diagnosis of musculoskeletal tumors. It is unclear which factors contribute the most to a successful biopsy. The aim of the study was to determine the value of ultrasoundguided core needle biopsy of solid lesions in the musculoskeletal system using a 16-gauge needle. Material and methods: A retrospective analysis performed at a regional sarcoma center over one year included patients referred for ultrasound-guided biopsy of musculoskeletal soft tissue lesions. At least 6 months’ clinical and radiological follow-up, results from repeat or excisional biopsy, or interventional treatment, served as outcome reference. The biopsy procedure and yield were analyzed. The biopsy was classified as ‘diagnostic’ when a definitive diagnosis could be made on the first biopsy, and ‘accurate’ when only the malignant or benign nature of the tumor could be determined. Results: From 102 referrals for biopsy of soft tissue lesions in 2019, a total of 73 biopsies of solid lesions with a 16-gauge cutting needle were included (73 patients). There were 34 males and 39 females, with a mean age of 57.7 years. The overall proportion of diagnostic biopsies was 84%, for malignant lesions 88% and benign lesions 81%. The tumor could be classified as malignant or benign in 12 patients (16%) (accurate biopsy). It was possible to discriminate between malignant and benign lesions in each case. The majority of biopsied lesions were benign 64% (n = 47). Conclusion: The diagnostic value of ultrasound-guided percutaneous core needle biopsy of musculoskeletal soft tissue lesions performed with 16-gauge needle is good, with a high rate of diagnostic biopsies, both for benign and malignant lesions.