Pure neuritic leprosy (PNL) is characterized by exclusive peripheral neuropathy without dermatological alterations. Diagnosis is difficult since skin lesions and acid-fast bacilli (AFB) in slit smears are absent. Presently, the gold standard for diagnosis is the histopathological examination of peripheral nerve biopsy. Even then, the detection of bacteria is difficult, and histological findings may be non-specific. Nerve biopsy is an invasive procedure that is possible only in specialized centers and limited to certain sensory nerves. Therefore, the establishment of serological, immunological, and molecular laboratory tests could be more beneficial for diagnosing pure neuritic leprosy to achieve effective treatment and reduction in its consequent disabilities. This review suggests that the presence of Mycobacterium leprae (M.leprae) in PNL cases can be proven by using non-invasive procedures, viz., multiplex polymerase chain reaction (M-PCR), serological findings, immunological profiling, and improved nerve-imaging. Findings also indicate the necessity for improving the sensitivity of PCR and further research on specificity in ruling out other clinical conditions that may mimic PNL.