We studied five cystic ovarian mucinous tumors with spindle cell mural nodules to define their histologic and immunohistochemical properties. Three of these mural nodules consisted of carcinomatous nests surrounded by highly pleomorphic polygonal and spindle cells. There were transition zones between the pleomorphic cells and the cell nests. In all three cases, both cell populations coexpressed cytokeratin and vimentin, suggesting a diagnosis of anaplastic carcinoma. A fourth nodule consisted of moderately differentiated adenocarcinoma embedded in prominent, cytologically uniform spindle cells. These cells were histologically distinct from the carcinoma; there were no zones of transition. The carcinoma was strongly positive for cytokeratin but only weakly positive for vimentin; the spindle cells expressed vimentin but not cytokeratin. We diagnosed this lesion as carcinoma with a reactive spindle cell stroma. A fifth mural nodule was composed entirely of interlacing fascicles of uniform spindle cells that were negative for cytokeratin but positive for vimentin, muscle-specific actin, and desmin; these findings support a diagnosis of leiomyoma. Two of the four patients with malignant nodules died of disease; the rest are alive and disease-free after follow-up intervals ranging from 1 to 4 years. This study demonstrates the usefulness of immunohistochemistry in distinguishing variant forms of spindle cell mural nodules in cystic ovarian mucinous tumors. It further suggests that malignant nodules do not necessarily carry a poor prognosis.