Joint involvement is unusual in patients with monoclonal gammopathies. It has been characteristically described as a rheumatoid-like seronegative polyarticular erosive arthropathy, which also has been related to crystal deposition of cryoglobulins in the synovium and several other tissues. This report describes the case of a 57-year-old African American woman with a seronegative polyarthritis associated with deposition of nonbirefringent or weakly positive birefringent rhomboid-shaped crystals in the synovial fluid. The patient, who was subsequently diagnosed with multiple myeloma, showed good clinical response to oral and intra-articular corticosteroids. Type II cryoglobulins were identified in the serum as well as in the synovial fluid. It is important to consider this association as part of the differential diagnosis of a patient with multiple myeloma and arthritis.