OBJECTIVE To explore the clinical features, treatment and prognosis of multiple myeloma (MM) with extramedullary plasmacytomas (EM). METHODS A total of 43 patients were enrolled and divided into 2 groups. Group-1 had 12 patients of EM occurring after the diagnosis of MM while Group-2 included 31 EM patients at the initial diagnosis of MM. RESULTS The male-to-female proportion was 23:20 and there was a median age of 53 years. The distribution of different isotypes was IgG (n = 15), IgA (n = 9), IgD (n = 2), κ light chain (n = 6), λ light chain (n = 6), biclonal myeloma (n = 3) and nonsecretory myeloma (n = 2). The sites of complicating plasmacytoma included skin, muscle and spinal canal. Nine patients received bortezomib plus DECP (cisplatin, etoposide, cyclophosphamide and prednisone) and 2 patients underwent traditional chemotherapy in Group-1. The outcomes were as follows: complete remission (CR, n = 2), partial remission (PR, n = 4) and death (n = 5). And 11 patients received traditional chemotherapy in Group-2, 7 attained PR and 4 died. Twenty patients received bortezomib plus other chemotherapeutic drugs in Group-2. The outcomes were as follows: CR (n = 12), PR (n = 7) and death (n = 1). The median overall survival (OS) was 36 months (range: 10 - 120) in Group-1 and 23 months (range: 5 - 52) in Group-2 respectively. In Group-1, the estimated 3- and 5-year OS were 54.21% and 27.10% respectively. And in Group-2, the estimated 3- and 4-year OS were 39.83% and 13.28% respectively. CONCLUSIONS The EM patients show aggressive, complicated and diverse clinical courses and the unusual manifestation of multiple organ involvement by plasma cells. Traditional chemotherapy has a poor efficacy and the prognosis is unfavorable, especially for EM with concurrent MM. The combined treatment of bortezomib with second-line chemotherapy may achieve curative effects.