Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and 
lower motor neurons. In the absence of any validated biological marker, the 
diagnosis of ALS depends upon recognition of characteristic symptoms and signs 
together with supportive electrophysiological findings. The diagnosis of ALS is 
easy to recognize in its fully developed form but during the early stages both 
false positive and false negative diagnoses are common. In clinical practice, 
diagnostic difficulties mostly arise with patients who present either with only 
upper motor neuron, or with only lower motor neuron signs. It may be difficult 
to distinguish ALS with clinically predominant lower motor neuron involvement 
from alternative diagnoses including spinal atrophies of adult onset, Kennedy's 
disease, inclusion body myositis and motor neuropathies with conduction blocks. 
The diagnosis of ALS related syndromes (progressive muscular atrophy, primary 
lateral sclerosis and progressive bulbar palsy) requires the elimination of 
alternate diagnoses. This paper reviews the main characteristics of diseases 
mimicking ALS and the atypical subsets of ALS.