Muscle pathology plays a central role in the diagnosis of muscle diseases. Proper handling, fixation and transportation of muscle biopsy specimens are necessary to avoid artifacts. Hematoxylin and eosin provides information on basic morphological abnormalities, including general structural changes, fiber size variation, necrosis and regeneration, endomysial fibrosis and lymphocyte infiltration. Modified Gomori trichrome is useful to detect abnormal structures including protein aggregates. NADH-tetrazolium reductase highlights intermyofibrillar network, thus serving to detect myofibrillar disorganization. Myosin ATPase is used for evaluating fiber types. Selective type 1 fiber atrophy reflects myopathic process while fiber type grouping reinnervating process. The final interpretation whether the biopsy demonstrates myopathic or neuropathic changes is based upon all these findings.