Abstract: Objective: To investigate the expression and its clinical significance of mutated/nonmutated (Codon 12) N- Ras and pERK1/2 (Extracellular signal- regulated kinase), in order to clarify the relationship between expression of Ras and ERK in Multiple Myeloma (MM). Methods: Western blot analysis was used to detect the expression level of N- Ras and pERK1/2, and mutation analysis at N-ras codon 12 was unished using the method of PCR/RFLP, PCR/SSCP and DNA sequencing analysis, in the clinical samples from 28 diagnosed MM patients. Results: The expression level of N- Ras and pERK1/2 (N-Ras: 0.56±0.19; pERK1/2: 0.39±).21) was significant higher in the clinical samples suffering from multiple myeloma than that in the group of peripheral blood lymphocytes of volunteer (N- Ras:0.13 ±0.12; pERK1/2: 0.10d0.14, P<0.01). There was no mutation at N- ras codon 12 in all of patients suffering from MM. Close relationship was found between the expression level of non-mutated N- Ras and pERK1/2 in Multiple Myeloma (r=5.1326, P<0.01). Conclusions: There is a close relationship between the expression of N- Ras and the pERK1/2 in Multiple Myeloma. Ras/ERK signaling pathway,seldom affected by N-ras (Codon 12) mutation, may play some roles in the development of human Multiple Myeloma.