A 66 years old Caucasian woman with pneumococcal meningitis was treated and discharged after an uncomplicated course. Five months later she was readmitted with fever and right side abdominal pain and diagnosed with pneumococcal spondylodiscitis. One year later she was treated for a severe chest X-ray confirmed left lobar pneumonia. Two years later she was diagnosed with a pneumococcal pneumonia in her left lung with septic shock. An immune deficiency screen revealed slightly reduced IgA levels, low IgG2 levels, low IgG3 levels and high IgG1 levels. No other immune defects were identified. She did not respond serologically on vaccination with 13-valent conjugate and 23-valent polysaccharide pneumococcal vaccines. Further evaluations revealed a positive M-component in her blood and a bone marrow biopsy diagnosed her to have monoclonal gammopathy of undetermined significance. To protect her against future life threatening pneumococcal infections she was started on treatment with intravenous immunoglobulin. The case report illustrates the importance of thorough evaluation of patients with unusual infectious disease entities or unusual frequency of infections in individual patients. To optimize prophylactic measures and active treatment options in the individual patient, it is important to identify underlying causes of diseases and immune deficiencies that potentially can lead to life threatening infections. This is illustrated in our case by an undiagnosed monoclonal gammopathy of undetermined significance in an apparently healthy woman with at least three life threatening documented pneumococcal infections in a two-year period and poor pneumococcal vaccine response.