Monomelic amyotrophy is a rare form of motor neuron disease usually presenting as painless asymmetric weakness and atrophy in the distal upper extremities of young adults. Only rarely are the legs involved and pyramidal findings are uncommon. Monomelic amyotrophy is most often observed in people of Japanese and Indian heritage and affects men almost exclusively. Most cases are sporadic. Laboratory testing is frequently normal or nonspecific except for electrophysiologic studies which typically demonstrate reduced compound muscle action potential amplitudes, fasciculations, and features consistent with acute and chronic denervation in distal upper extremity muscles. Necropsy in 1 patient identified anterior horn cell shrinkage, necrosis, and gliosis in appropriate spinal cord segments. Symptoms and signs often progress for several years before spontaneously arresting. The differential diagnosis for monomelic amyotrophy is broad, including processes which affect the cervical cord, roots, brachial plexus, and individual or multiple nerves in the upper extremity.