Background: Ly-9 (CD229) and SLAMF7 (CD319) are more stable markers that could be used to replace the less stable conventional markers CD138 and CD38 in multiple myeloma (MM) patient follow-up. In those patients, the correlation between these markers and the histopathologic marker c-Maf has not been well investigated. Objective: To assess the predictive value of CD229, CD319, and c-MAF overexpression on outcome of treatment in MM patients. Patients and Methods: 61 newly diagnosed multiple myeloma patients were involved in this prospective study. Flow cytometric analysis of bone marrow (BM) samples for CD229 PE, CD319 PE, CD138 PerCP and CD38FITC as well as BM biopsy immunohistochemically were analyzed for c-Maf expression Results: CD229 and CD319 were highly expressed in (≥93.95%) and (≥95.6%) of MM patients respectively. c-Maf was positive in (29.5%) of patients. In MM patients with high expression of CD229 and CD319 as well as those with c-Maf positivity showed high serum Ca⁺⁺, β2M, CD138 and CD38. CD229 was significantly correlated with CD319, CD38, CD138, β2M and serum Ca (p-values were< 0.001,0.01, 0.01, 0.009, and 0.02 respectively). Patients with overexpression of CD 229, CD319 and c-Maf were more refractory to treatment (p-values were <0.001,<0.001 and <0.001 respectively). Conclusion: We detected that both CD229 and CD319 were significantly overexpressed on MM cells and correlated significantly with CD138 and CD38, suggesting their use as alternative markers for MM diagnosis as well as follow-up. Patients with CD229,CD319, and c-Maf overexpression were associated with a significant poor response to therapy.