Cerebellar ataxia-predominant multiple system atrophy (MSA-C) and cortical cerebellar atrophy are representative diseases of adult-onset sporadic degenerative ataxia. Both diseases are distinctly different because of α-synuclein pathology. However, it takes approximately 2 years for cerebellar ataxia to progress to concomitant severe autonomic dysfunction in patients with MSA-C. The period of only cerebellar ataxia (mono system atrophy) may extend to more than 10 years. Understanding mono system atrophy is vital for the early diagnosis and drug development for MSA. In this review, we discuss mono system atrophy focusing on the concept and natural history and the possibility of the of early diagnosis and disease-modifying therapy for MSA.