To establish xenotransplated mouse model by non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice with primary myeloma cells. The model of xenograft was established in NOD/SCID mice by tail vein injection of mononuclear cells from two end stage multiple myeloma patients, three mice were inoculated for each patient. Mice were monitored weekly for body weight. Two weeks later, the human CD45(+) cells from peripheral blood of mice were evaluated by flow cytometry (FCM). The experiment endpoint was body weight loss up to 20% or had pale, vertical hair and listlessness, then spleen and liver were studied by histologic analysis, the human CD45(+)CD38(+) cells from spleen, lymph node, peripheral blood and bone marrow were evaluated by FCM. Body weight of mice in group patient 1 and group patient 2 decreased seven and five weeks after inoculation respectively; the human CD45(+)CD38(+) cells appeared in the peripheral blood (26 ± 4) and (16 ± 4) days after inoculation in group patient 1 and group patient 2 respectively, and increased by time, reaching (16.2 ± 3.0)% and (31.3 ± 3.5)%, respectively at the endpoint; the spleen, liver and lymph node of both groups enlarged, the typical malignant plasma cells were observed in them. The human CD45(+)CD38(+) cells were detected in spleen, lymph node and bone marrow by FCM. Our study successfully established a NOD/SCID mouse model xenotransplated with human primary myeloma cells.