Background The use of computed tomography (CT) for image guidance during biopsies is a powerful approach. The method is, however, often associated with a significant level of radiation exposure to the patient and operator. Purpose To investigate if a low-dose protocol for CT-guided musculoskeletal (MSK) biopsies, including a combination of different radiation dose (RD) techniques, is feasible in a clinical setting. Material and Methods Fifty-seven patients underwent CT-guided fine-needle aspiration cytology (FNAC) utilizing the low-dose protocol (group A). A similar number of patients underwent CT-guided FNAC using the reference protocol (group B). Between-group comparisons comprised radiation dose, success rate, image quality parameters, and workflow. Results In group A, the mean total dose-length product (DLP) was 41.2 ± 2.9 mGy*cm, which was statistically significantly lower than of group B (257.4 ± 22.0 mGy*cm), corresponding to a mean dose reduction of 84% ( P<0.001). The mean CTDIvol for the control scans were 1.88 ± 0.09 mGy and 13.16 ± 0.40 mGy for groups A and B, respectively ( P < 0.001). The success rate in group A was 91.2% and 87.9% in group B ( P = 0.56). No negative effect on image-quality parameters, time of FNAC, and number of control scans were found. Conclusion We successfully developed a low-dose protocol for CT-guided MSK biopsies that maintains diagnostic accuracy and image quality at a fraction of the RD compared to the reference biopsy protocol at our clinic.