Objective To investigate the clinical characteristics, treatment and prognosis of multiple myeloma (MM) with extramedullary infiltration. Methods The clinical data of 43 patients with MM with extramedullary infiltration admitted to our hospital from May 2005 to December 2010 were retrospectively analyzed. There were 12 cases with extramedullary infiltration during the course of MM (group 1) and 31 cases with extramedullary infiltration at the time of MM diagnosis (group 2). Results The median age of the patients in this group was 53 years (28-76), 23 males and 20 females. 15 cases of IgG type, 9 cases of IgA type, 2 cases of IgD type, 6 cases of k-light chain type, 6 cases of l-light chain type, 3 cases of biclonal type, and 2 cases of nonsecretory type. The most frequently infiltrated sites were skin and muscle soft tissues (39 cases), deep soft tissues (16 cases), and intravertebral canal (18 cases). Of the 9 patients in group 1 treated with bortezomib combined with DECP regimen chemotherapy, 2 achieved complete remission (CR), 4 achieved partial remission (PR), and 3 died of disease progression; 2 patients treated with conventional chemotherapy both progressed to death; and 1 died after abandoning treatment. In group 2, 11 patients were treated with conventional chemotherapy, 7 achieved PR and 4 died. 20 patients were treated with bortezomib-based combination chemotherapy, 12 achieved CR, 7 achieved PR, and 1 died. The median survival was 36.5 (10-120) months in group 1 and 23 (5-52) months in group 2. Conclusion Patients with MM with extramedullary infiltration have complex clinical manifestations and poor prognosis, and better outcomes can be achieved with bortezomib-based treatment.