Objective To assess the efficacy and cost of a new frontloading biopsy system, Spirotome® (system 1), in musculoskeletal lesions, and to compare the results with those obtained with commonly used biopsy devices. Methods System 1 was used in all soft tissue lesions (STL) and osteolytic bone lesions (OBL) of patients who presented at our department for CT-guided biopsy between January 2009 and June 2010. Accuracy and cost were compared to those of Bonopty® (system 2) and Tru-cut (system 3) procedures. Results The efficacy of system 1 was 85% in STL and 89% in OBL. The procedure was well tolerated and caused no complications. System 3 had an efficacy of 84% in STL and OBL combined. The efficacy of system 2 in OBL was 85%. The cost of single-use system 1 and system 2 was comparable, the cost of system 3 and multiuse system 1 compared to single-use system 1 was 25 and 7%, respectively. Conclusions The efficacy of system 1 in biopsy of STL and OBL was better than that of system 3. In OBL, the efficacy of system 1 was better than that of system 2. In STL at hazardous locations and small OBL with a thin cortical shell, system 1 offers the advantage of variable length and controlled loading. In these cases, single-use system 1 was cost-effective when compared to surgical biopsy. The cost per procedure of multiuse system 1 was lower than of system 3.