Gastroesophageal-vulvar leiomyomatosis represents a rare syndrome of diffuse smooth muscle proliferation primarily in the gastroesophagus and vulva. To our knowledge, there are 19 cases reported in the literature, most associated with Alport's syndrome. We recently encountered a case not associated with Alport's syndrome, which had progressed over the course of 20 years. We used immunohistochemistry to further delineate the process. Leiomyomatosis appears to be a systemic disorder, with indolent proliferations of smooth muscle in areas that may not be clinically significant.