To determine the cellular origin of plasmacytoid cells in salivary gland adenomas, immunohistochemistry was performed on sections from 12 pleomorphic adenomas rich in these cells. In normal salivary glands included in these sections, the myoepithelial cells (MECs) expressed alpha-smooth muscle actin (alphaSMA) and smooth muscle myosin heavy chain (SMMHC), whereas the duct luminal cells expressed keratins 19, 18 and 8. Some of the salivary duct basal cells expressed these keratins, and the acinar cells expressed keratins 18 and 8. The expression profile was similar in rat salivary glands not only after but also during development. The immature MECs never expressed the keratins nor did the immature duct cells express alphaSMA. In seven cases, up to 60% of the plasmacytoid cells expressed keratin 19. In three of these cases, about 10% of the plasmacytoid cells expressed keratin 18. No plasmacytoid cells expressed alphaSMA, SMMHC or keratin 8. These results indicate that plasmacytoid cells originate from luminal cells and not from MECs. Furthermore, in addition to the luminal tumor cells, the non-luminal cells could express keratins 19, 18 and 8. Therefore, it is necessary to re-evaluate the prevailing notion that non-luminal cells are modified MECs. Keratin 14, basic calponin, vimentin and p63 were bi-specific for the MECs and the duct cells. Therefore, expression of these proteins by significant numbers of the non-luminal tumor cells and the plasmacytoid cells never denied the above notion.