Multiple myeloma associated with infectious spondylitis at initial presentation is rare. We report a previously healthy woman with back pain for 3 weeks, initially diagnosed as Escherichia coli infectious spondylitis. Because magnetic resonance imaging revealed skip lesions other than infectious spondylitis, extensive work-up disclosed monoclonal immunoglobulin G kappa and 30% plasma cells in bone marrow. The patient was treated with antibiotics for 8 weeks without recurrence in the subsequent 6 months. Although the panorama of infectious spondylitis was obvious and substantial, our case demonstrates that further investigations for underlying diseases are critical, especially when image findings are incompatible with common presentations of infectious spondylitis.