The stromal cells of three cystosarcoma phyllodes, five typical fibroadenomas, and one juvenile fibroadenoma were studied by light and electron microscopy. Immunohistochemical staining for the S-100 protein also was performed on tissues from each of the three categories. On ultrastructural examination, cells comprising the three varieties of lesions were similar. Cells with fibroblastic features predominated in all cases. Myoid differentiation was present in two cases, one of cystosarcoma and one of fibroadenoma. Junctional complexes were present in the cystosarcomas but not in the fibroadenomas. Basal lamina was focally present around stromal cells in the cystosarcoma phyllodes but was not evident around cells of the typical fibroadenomas or the juvenile fibroadenoma. Stroma cells of the fibroadenomas and the cystosarcoma phyllodes did not stain for S-100 protein. The results support the hypothesis that the proliferating cells in all three tumor categories are similar and have features of fibroblasts. The lack of staining for S-100 protein would suggest an origin different from the myoepithelia. The latter conclusion, however, must be interpreted with a degree of reservation as we have shown that not all myoepithelial cells stain with certain monoclonal antibodies directed against the α and β chain of S-100 protein. © 1987 W. B. Saunders. All rights reserved.