Background: Cases with pure neural leprosy (PNL) are difficult in their diagnosis and usually loss the early management opportunity. Objective: to evaluate Real time PCR and high resolution ultrasonography of peripheral nerves as diagnostic tools in PNL. Methodology The study included 25 suspected PNL and 25 healthy controls. All patients were subjected to ultrasonography cross-sectional area (CSA) measurement. Fine needle aspiration (FNA) was obtained, and followed by Ziehl-Neelsen (ZN) staining, and real time PCR. Results: ZN staining demonstrated M leprae bacilli in only 8 cases while their DNA was detected in 92 % cases (Sensitivity of both were 100%, and 44.4%, respectively). Only the left median and right and left posterior tibial nerves CSA measurements showed good performance in distinguishing patients of PNL. Median nerve cut off=15.5 mm2 , with a sensitivity of 72%), and right and left posterior tibial nerves CSA Cut Off were 12, 11.5 mm2 with sensitivity of 76-84%. Conclusions: ultrasonography of suspected nerves and real time PCR of nerve aspirates are simple accurate tests for diagnosis of PNL.