The signet-ring stromal tumor of the ovary, described only twice previously, is an enigmatic lesion in respect to its cell lineage and the nature of the cytoplasmic vacuoles that cause the signet-ring cell appearance. The vacuoles were shown in the initial report to contain no lipid, mucoprotein, or glycogen, and the ovarian stromal cell was assumed to be the cell of origin. The present study describes three ovarian neoplasms in which the immunohistochemical and ultrastructural findings support a stromal origin for the cells, and a fourth tumor that simulated the other three closely on light microscopic examination but had several features supporting a sex-cord rather than stromal origin: immunohistochemical staining for keratin and alpha smooth muscle actin, and globular keratin staining, similar to that seen in granulosa cell tumors; and numerous prominent junctions including desmosomes on electron microscopy. In only one of the four tumors were the vacuoles similar ultrastructurally to those in the first reported case, appearing to result from generalized edema of the cytoplasmic matrix. In a second tumor, the vacuoles resulted from hydropic swelling of numerous mitochondria, which filled the cytoplasm of the cells. In the other two tumors, the vacuoles were not cytoplasmic, but cytoplasmic pseudoinclusions of edematous extracellular matrix. An additional interesting finding in one of the four tumors was the presence of hyaline globules within and adjacent to the signet-ring cells. Ultrastructural examination revealed the globules to be degenerating erythrocytes, many of which had been phagocytosed by the tumor cells.