Background: The surface antigen CD319 (SLAMF7) is a marker of normal and malignant plasma cells in plasma cell myeloma. In view of the potential therapeutic use of SLAMF7‐targeting antibodies, such as elotuzumab, the detection of SLAMF7 expression levels on abnormal plasma cells might play an important role in the evaluation of therapy responses. Objective: This study aimed to evaluate role of CD319 marker in diagnosis and prognosis of plasma cell myeloma patients. Patients and Methods: The study was Cohort study conducted on newly diagnosed plasma cell myeloma patients in Clinical Pathology Department and Internal Medicine Department-Hematology Unit at Zagazig University Hospitals in period between February 2019 and February 2021. It included 18 cases diagnosed according to clinical, pathological, morphological and immunophenotypic criteria. Follow up of patients was carried out after 3 months of initiation of treatment to assess response to therapy. Results: This study showed that CD319 (SLAMF7, CRACC, CS1) is a stable marker with high expression mean fluorescence intensity (MFI) on normal and malignant plasma cells. In this study, CD319 is found positive in all plasma cell myeloma (PCM) patients. Low expression of CD319 (if MFI below 128.3) was associated with a significant better response to treatment and good prognosis but high expression of CD319 was accompanied by bad response to treatment. It can be effectively used as a diagnostic and prognostic marker for PCM. Conclusion: CD319 is found positive in all PCM patients. It can be effectively used as a diagnostic marker for PCM. Low expression of CD319 is associated with a significant better response to treatment and good prognosis. This indicates importance of CD319 as a prognostic marker of PCM.