Objective: In this study, we purpose to study the diagnostic accuracy and other diagnostic values (diagnostic yield, error, complication) of CNB without real-time image-guidance in out-patient clinic by comparing with open incisional biopsy in musculoskeletal sarcoma patients. Methods: We retrospectively reviewed the biopsy cases of sarcoma patients since 2002-2011 from medical records and histopathology database. The diagnostic accuracy in 4 aspects of histopathology: nature (benign or malignant), specific diagnosis, histological type, and histological grade between 2 methods were compared statistically, the gold standard were the histopathology from resected specimens while definite surgery and information of clinicoradiographic/laboratory by clinical course. The other diagnostic values (diagnostic yield, error, complication) were also compared between both methods. Results: There were 200 cases (open incisional biopsy 105 cases and CNB 95 cases). The diagnostic accuracies of open incisional biopsy were 97.14% for nature, 89.52% for specific diagnosis, 89.52% for histological type, 88.57% for histological grade and the diagnostic accuracies of CNB were 96.84%, 89.47%, 88.42%, 86.32% respectively. There were no statistically significant different between 2 methods in all histological aspects (nature; P-value = 0.901 95%CI = -0.432 to 0.380, specific diagnosis; P-value = 0.991 95%CI = -0.227 to 0.224, histological type P- value = 0.803 95%CI = -0.250 to 0.193, and histological grade; P-value = 0.63 95%CI = -0.261 to 0.158). The diagnostic yields of both methods were 98.13% for open incisional biopsy, 97.94% for CNB. It was no statistically significant different also as shown in table 6 (P-value = 0.919 95%CI = -0.469 to 0.520). There were 6 cases (3%) for overall major errors, 3 cases (2.86%) for open incisional biopsy and 3 cases (3.16%) for CNB. There were 18 cases (9%) for minor errors, 9 cases (8.57%) for open incisional biopsy and 9 cases (9.47%) for CNB. There was no related biopsy complication in both methods. Conclusion: The office-based CNB for diagnosis musculoskeletal sarcoma can achieve the acceptable high diagnostic accuracy rates comparing with the open incisional biopsy.