A 12-year-old, female spayed Chihuahua was diagnosed with nonsecretory multiple myeloma on the basis of multiple osteolytic lesions, histological evidence of plasma cell infiltrate on a bone biopsy, and absence of a monoclonal protein on serum and urine electrophoresis. A 6-week course of prednisone therapy resulted in no clinical improvement and the dog was euthanized 2 weeks after presentation because of progressive neurological impairment. Bone marrow specimens were processed and stained for ultrastructural and immunohistologic evaluation. Staining with antisera to immunoglobulin (Ig) G, IgM, and IgA was negative. Tumor cells in both the pelvic and rib masses displayed prominent reactivity with an antibody specific for a canine beta 1 integrin similar to VLA-4; however, the tumor cells failed to stain with antibodies known to react predominantly with antigens on B-lymphocytes (major histocompatibility complex class II, CD45RA, and CD21) or T-lymphocytes (Thy-1). The tumor cells also failed to stain with an antibody specific for the beta-subunit (CD18) of the leukocyte integrins (D11/CD18). Ultrastructural studies performed on bone marrow specimens revealed a pleomorphic population of plasma cells with moderate amounts of rough endoplasmic reticulum, erythrophagocytosis, and lack of crystalline inclusions.