Immunocytochemistry (ICC) proved to be an essential adjunct in the fine-needle aspiration (FNA) cytological diagnosis of chordoma of the clivus in a 62-year-old woman. The cytological picture in routinely stained smears was not entirely diagnostic for chordoma due to the paucity of typical 'physalipherous' cells. To exclude other primary or metastatic neoplasms of the skull base possibly sharing the same cytological picture, additional direct smears were immunostained with antibodies specific for cytokeratin (CK), vimentin (VIM), S100 protein (S100P), carcinoembrionic antigen (CEA), epithelial membrane antigen (EMA), glial fibrillary acidic protein (GFAP), CD68 antigen (KP1) and with the 'panepithelial' antibodies B72.3 and Ber-EP4. Chordoma cells showed the following immunoprofile: CK+/VIM+/S100P+/CEA-/EMA+/GFAP-/B72.3-/Ber-EP4-/CD68+. The pattern of immunoreactivity for CK, S100P and CEA confirms previously reported data, while the B72.3-/Ber-EP4-/CD68+ staining profile represents a novel observation. The detection of a CK+/S100+/CEA-/B72.3-/Ber-EP4- immunocytological profile of chordoma cells in aspirates is a basic requirement to exclude pertinent diagnostic differentials, such as metastatic carcinoma, ependymoma and sarcoma, and permits a reliable pre-operative diagnosis of the tumour by aspiration cytology.