To investigate the expression of extracellular matrix protein Reelin (RELN) and its relationship with the prognosis of patients with multiple myeloma. The mononuclear cells were collected from bone marrows of multiple myeloma patients by Ficoll gradient density centrifugation, the CD138+ cells were then purified by flow cytometry, the mRNA level of RELN was detected by real time PCR. The myeloma patients were divided into 2 groups according to the relative expression levels of RELN. Then the relationship of RELN expression level with clinical data was analyzed statistically. The high expression of RELN significantly correlated with the percentage of CD138+ cells, progress-free and total survival, but did not correlate significantly with DS (P>0.05) and ISS stages (P>0.05). The RELN high expression group showed higher levels of serum M protein, uric acid and serum calcium, lower hemoglobin, and more abnormal FISH results (including RB1 deletion, 1q21 amplification, IgH recombination, P53 deletion, D13S319 deletion) than those in RELN low expression group. Reelin correlates with the progression of multiple myeloma.