We describe the first report of plexiform lipoleiomyoma with amyloid stroma. A 57-year-old woman underwent an abdominal hysterectomy for methrorragia. The hysterectomy specimen exhibited a soft, rubbery, encapsulated 11 cm ovoid mass with aciniform, white cut surface on the right edge of the uterus. The histology was distinctive and typical of plexiform lipoleiomyoma: long cords, strands and small nests of cells embedded in a collagenous matrix. The neoplastic cells showed eosinophilic cytoplasm, crumpled, bland nuclei. Scattered islands of mature adipocytes were distributed throughout the leiomyomatous proliferation. Immunohistochemistry showed positivity for smooth muscle actin in the plexiform component, and for S100 in the adipocytes. Histogenesis and origin of the cellular neoplastic component are discussed.