Background and Objective: World Health Organization (WHO) describes two types of plasmacytomas which are solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (EMP). 17% to 33% of plasmacytomas, will progress into multiple myeloma (MM). The early diagnosis is very important as the plasmacytoma may be primary or metastatic lesion of MM. Prognosis of solitary plasmacytoma could be worse if it recurred as in case of its evolution toward systemic MM. Methodology: 10 patients with plasmacytoma in the National Cancer Institute and Histopathological laboratory of Minia University were analyzed immunohistochemically for detection of syndecan-1 as a diagnostic marker for plasmacytoma and detection of plasmacytoma behavior through interpretation the expression of both CD117 and CD56. Results: All cases showed strong positive immunoreaction for Syndecan-1(grade 3) according to scoring system for immunohistochemical expression. The expression of CD117 in plasmacytoma was similar to the expression of CD56, (60%) showed grade 1, while (40%) were grade 0. Conclusion: We concluded that the importance of histopathological biopsy for early diagnosis and prognostic evaluations are important in that the plasmacytoma may be a primary or metastatic lesion of MM. and Syndecan-1can be used as diagnostic marker for plasma cells, while CD56 and CD117 expressed only in neoplastic plasma cells and their expression indicate good prognosis.