We report the case history of a 31-year old woman with a rare morphologic form of nodular sclerosing Hodgkin disease (NSHD) termed "syncytial variant." Its histologic features mimic metastatic carcinoma, thymoma, melanoma, non-Hodgkin lymphoma and germ-cell tumor. Antigens expressed on Reed-Sternberg cells, the hallmark of Hodgkin disease, and other neoplastic cells were screened to determine the correct diagnosis. This patient demonstrates the importance of using specific immunohistochemical techniques to clarify the diagnosis of NSHD of the "syncytial variant" subtype.