Background: Leprosy is a chronic infectious disease where delay in diagnosis or treatment can lead to deformities and disabilities for the rest of the patient's life. Definite diagnosis of leprosy has long been based on clinical picture, histopathology and/or the detection of acid-fast bacilli (AFB) from tissue smears or tissue sections stained by Ziehl-Neelsen. Aim of the work: We evaluated in this study, the usefulness of PCR for detection of M.leprae in the serum, as less invasive technique, in comparison to skin slit smear for the diagnosis of leprosy. Patients and Methods: This study included 30 non-treated patients of leprosy (9 multibacillary, 21 paucibacillary) skin slit smears had been taken. In addition, serum samples had been collected for polymerase chain reaction [PCR] test. Results: Negative Slit Skin Smear for AFB had been obtained in 20 cases with a rate of positivity of 33%. Serum PCR was positive in 20 patients giving an overall rate of positivity of 67% which confirm the diagnosis in 11 out of 20 cases with slit skin smear [SSS] negative. Conclusion: PCR does show to be more sensitive than slit skin smear [SSS] indicating its future use for diagnostic purposes especially in early leprosy cases.