Background: One predictive factor for patients with Mantle cell lymphoma has been identified as cyclin D1 expression. Nonetheless, there is ongoing discussion on the prognostic significance of Cycline D1 overexpression in multiple myeloma. As far as we are aware, this work has never been completed at Zagazig University's Faculty of Medicine. The purpose of this research was to assess the clinical relevance of Cyclin D1 expression in multiple myeloma. Methods: This cohort study was conducted on newly diagnosed plasma cell myeloma (PCM) patients in clinical pathology Department and Internal Medicine Department–Hematology unit at Zagazig University Hospitals and included 52 cases diagnosed according to clinical, pathological and morphological criteria. Follow up patients was carried out for 3 months from initiation of treatment to assess response to therapy. Results: Cyclin D1 is a stable Immunohistochemical marker with strong expression on plasma cells and there was highly statistically significant strong positive correlation between Cyclin D1 expression and increasing percentage of plasma cells, increasing CD138 expression on BMB. As regard response to treatment there was a statistical significant increase in Cyclin D1 expression percent among cases with progressive disease compared to cases with complete and partial response. Conclusion: Cyclin D1 had a clinical significance in PCM patients and could be used as a prognostic marker in addition to traditional markers