Plasmacytoma is a rare neoplastic disorder arising from B-cell series lymphocytes. It can develop in three clinical variants: a) Multiple Myeloma (M.M.); b) Solitary Plasmacytoma of the bone; c) Extramedullary Plasmacytoma (EMP). EMP generally occurs in the submucosal tissue of the upper airways (80% of cases). This paper reports 22 cases of EMP of the head and neck observed in the last 20 years and reviews pertinent Literature. Four of our cases were located in the nasopharynx, four in the oropharynx and five in naso-sinusal sites. More rarely, the lesion occurred in the larynx (2 cases) or in the oral cavity (3 cases). In 4 patients multiple localizations in the upper airways were observed. Full evaluation was carried out in order to exclude disseminated disease. With the exception of 2 cases which were surgically treated, radiotherapy (RT) represented the treatment of choice in all patients, with doses ranging from 36 to 58 Gy. In 9 cases RT was administered after complete surgical resection. Follow-up time ranged from 13 to 167 months (mean 69.6). A partial response after treatment was observed in 4 cases. In only two of these cases neoplastic residue was observed (further RT allowed complete remission of the disease). In the other two cases, residual masses consisted in amyloid deposits. Three patients developed disseminated disease (MM) after a disease-free period ranging from 3 to 6 years. Five-year actuarial disease was 92%. Although surgery is generally considered a diagnostic tool, in our opinion local disease should always be removed surgically when surgery produces low morbidity. Surgical debulking of the lesion can increase the probability or local radiotherapeutic control.