Clinical, histopathological, and EM findings are described for two Cairn terrier litter mates, an 18‐month‐old male and an 11‐month‐old female with progressive neuronopathy. The initial clinical signs were characterized by hind limb weakness and ataxia, which deteriorated with exercise. These signs progressed over several months to tetraparesis. Pathological examination revealed extensive chromatolytic degeneration of neurons and moderate secondary Wallerian‐type degeneration in the spinal cord and brain stem. Progressive neuronopathy can be differentiated clinically from globoid cell leukodystrophy, another progressive neurological disorder in Cairn terriers, by the exercise‐induced deterioration of the neurological signs. Progressive neuronopathy occurs only in Cairn terriers and because of the similarity in age of onset and the occurrence in one litter, an inherited disease is suspected.