Satoyoshi syndrome is a rare, slowly progressive disorder of unknown etiology with a poor long-term prognosis. The syndrome consists of the following clinical features: (1) painful, intermittent muscle spasms; (2) alopecia; (3) diarrhea; and (4) skeletal abnormalities in cases of juvenile onset. The age of onset is typically less than 20 years of age, although three adult onset cases had been reported. There had been no case report of Satoyoshi syndrome with strict unilateral presentation. We present a 25-year-old man with progressive unilateral hair loss and muscle spasms. Although previous literature had postulated malabsorption and autoimmune mechanism as pathogenic for Satoyoshi syndrome, the presence of a strictly unilateral presentation argues against those hypotheses. However, these hypotheses should still be considered, as our patient did not fit a typical Satoyoshi syndrome. Therefore, more research is needed to understand the pathophysiology and develop an effective treatment to prevent the progression of the disease.