Pleural tuberculosis (pTB) is a very common form of extrapulmonary tuberculosis (TB). Its diagnosis presents worldwidea major burning challenge due to the limitations of available conventional diagnosis tools. These latter include microscopic examination of the pleural fluid for acid-fast bacilli, mycobacterial culture of pleural fluid in solid or liquid media, sputum or pleural tissue, and histopathological examination of pleural tissue; these tests have recognized limitations for clinical use. Hence, to overcome these limitations, attention has been devoted to new nucleic acid amplification (NAA) diagnosistests such as the polymerase chain reaction (PCR) and real-time PCR (RT-PCR), owing to their accuracy, rapidity, high sensitivity and specificity. Within this context, this prospective study was conducted to evaluate the performance of molecular diagnosis methods for differentiation between tuberculosis and non-tuberculosis pleural effusions. Fifty patients with pleural effusion were enrolled in this prospective study in Rabat, Morocco. The efficacy of conventional polymerase chain reaction (PCR) in the diagnosis of tuberculous pleurisy by targeting IS6110 and mycobacterial internal transcribed spacer(MYITS) was evaluated against histopathologic examination and culture results.Our results showed that IS6110 PCR could “rule in” pTB, the sensitivity and specificity being 41.6 % and 85.7 % respectively.Therefore, the findings confirmed that molecular tests have a relatively high specificity in EPTB but lower sensitivity, thus a positive test is treated as a pTB case whereas negative one cannot exclude the disease. Although the study was limited by small sample size, it adds to the body of evidence of usefulness of molecular testing as adjunctsto histopathologic examination for accurate diagnosis of pTB, to treat timely and to avoid the emergence and spread of drug resistant pTB. However, further efforts should be made to increase the sensitivity of NAA methods and to identify the best molecular targets to be useful in clinical practice.