Background: The diagnosis of osteoarticular tuberculosis is clinico-radiological in endemic areas. However every patient does not have the classical picture. Osteoarticular tuberculosis is a paucibacillary disease hence bacteriological diagnosis is possible in 10-30% of the cases. The present study is undertaken to correlate clinico-radiological, bacteriological, serological, molecular and histological diagnosis. Materials and Methods: Fifty clinico-radiologically diagnosed patients of osteoarticular tuberculosis with involvement of dorsal spine (n = 35), knee (n = 8), shoulder (n = 1), elbow (n = 2) and lumbar spine lesion (n = 4), were analyzed. Tissue was obtained after decompression in 35 cases of dorsal spine and fine needle aspiration in the remaining 15 cases. Tissue obtained was subjected to AFB staining, AFB culture sensitivity, aerobic/anaerobic culture sensitivity histopathological examination and polymerase chain reaction (PCR) using 16srRNA as primer. Serology was performed by ELISA in 27 cases of dorsal spine at admission and one and three months postoperatively. Results: AFB staining (direct) and AFB culture sensitivity was positive in six (12%) cases. Aerobic/anaerobic culture sensitivity was negative in all cases. Histology was positive for TB in all the cases. The PCR was positive in 49 (98%) cases. All dorsal spine tuberculosis cases showed fall of IgM titer and rise of IgG titer at three months as compared to values at admission. Conclusion: Histopathology and PCR was diagnostic in all cases of osteoarticular tuberculosis. The serology alone is not diagnostic.