Background: Diagnostic rationale of tuberculosis as a specific epidemiological endemic disease depends mainly on clinical signs over and above microbiological and histopathological findings. Purpose: The aim of this study is to differentiate between histopathological features of pulmonary parenchymal cavitary tuberculosis in accordance with different biopsy techniques; fiberoptic bronchoscopic bronchoalveolar lavage, transbronchial lung biopsy, percutaneous guided biopsy (CT computed tomographic/ultrasound). Patients and methods: Forty-one patients with pulmonary parenchymal cavitary lesions confirmed to be tuberculous by sputum Ziehl Neelsen staining undertook antituberculous therapy without improvement. Tissue biopsy samples were obtained from radiological shadows by different methods and studied regarding histopathological findings. Results: Caseating granuloma showed higher diagnostic accuracy in percutaneous biopsy and in open biopsy followed by BAL/TBLB (100% and 80% respectively) while noncaseating granuloma was detected in 20% of broncheoalveolar lavage and transbronchial lung biopsy BAL/TBLB only. Inflammatory smear prevailed in 86.66% of patients who performed BAL/TBLB but was absent in open and percutaneous guided biopsy, on the one hand, smear cellularity of moderate quantity showed higher percentage in percutaneous guided biopsy (88.24%) followed by BAL/TBLB (80%) lastly open biopsy (66.66%). Other pathological findings predominated in patients who had undertaken open biopsy as tuberculous lymphadenitis (55.55%) and interstitial fibrosis (55.55%). Significant statistical differences were found in all pathological lesions (p = 0.00). Conclusion: Differentiation between histopathological patterns of parenchymal cavitations symbolizes an important clue about the accuracy of diagnosis between the biopsy methods.