In 55 cases presenting with enlarged peripheral nerves without any skin lesions, a rice grain-sized biopsy of the nerve lesion was taken for histopathological examination. As a result definitive diagnoses could be established: leprosy was diagnosed in 32 cases. In 23 cases the cause of nerve enlargement was not leprosy: post-traumatic neuritis 9, cysts 5, hypertrophic neuritis 3, nonspecific 4, neurofibroma 1, and amyloidosis 1. In all of these cases there was a deficit of the nerve function and postoperatively there were no complications. The authors, as a result of this experience, believe that surgical exploration and biopsy is a harmless diagnostic tool for establishing a definitive diagnosis of leprosy in cases presenting with enlarged peripheral nerves without any skin lesions. In 23 out of 55 such cases the nerve enlargement was proved to be other causes than leprosy.