This study aimed to investigate patient-specific, lesion-related, and technical factors that potentially influence diagnostic yield of computed tomography (CT)-guided biopsies of bone lesions. The nondiagnostic biopsy rate of long bone lesions was higher than that of other bone lesions (odds ratio, 3.46; 95% confidence interval, 1.32-9.09). Magnetic resonance imaging was obtained before biopsy in significantly more nondiagnostic cases compared with diagnostic cases (P = 0.027). Computed tomography-guided biopsies had a nondiagnostic rate of 19.87%, and lesions in the long bones of the extremities were disproportionately common among this group. There was no significant association between biopsy results and several patient-specific, lesion-related, and technical factors.