Amyotrophic lateral sclerosis (ALS) is an age‐associated neurodegenerative disease that primarily involves the motor neuron system. Despite this disease having been studied for over 100 years, its etiology is still unknown and no specific diagnostic laboratory test is available. The diagnosis of ALS is therefore based on clinical and/or neuropathological findings with loss and degeneration of the large anterior horn cells of the spinal cord being the principal and most salient features. Several symposia and workshops on the cytopathology of ALS were held within the last 2 year period, which reflects the many new and important developments taking place. Although loss of motor neurons has been well‐known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by applying immunohistochemical and electron microscopic procedures. The purpose of this review is to introduce some of the novel findings associated with lower motor neuron alterati