Septic arthritis induced by Streptococcus pneumoniae is an uncommon manifestation of pneumococcal infection. Pneumococcus has been identified as the inciting pathogen in only 6% of cases of septic arthritis in recent retrospective studies (Ross et al., 2003). Approximately 50% of patients with pneumococcal septic arthritis have a preceding or concurrent extra-articular focus of infection. The septic joint evolves from hematogenous seeding of the highly vascular synovial membrane by bacteria. Polyarticular disease occurs in only approximately 36% of patients. Most pneumococcal septic arthritis occurs with coexistant joint disease, prosthesis, alcoholism, HIV infection, or rheumatoid arthritis (Baraboutis & Skoutelis, 2004; Raad & Peacock, 2004). We report a case of polyarticular septic arthritis as the first manifestation of an underlying disease. Our literature review discloses that this is the first reported case of multiple myeloma initially presenting as pneumococcal septic arthritis in the USA and the third internationally (Cuesta et al., 1992; Renou et al., 2007).