Stenotrophomonas maltophilia is a bacterial pathogen that can be fatal in hospitalized and immunocompromised patients with mortality as high as 69%. Risk factors for infection include those apparent in many pediatric cancer patients. Treatment is challenging as S. maltophilia is resistant to several antibiotics. Furthermore, the presentation of soft tissue infection in neutropenic patients may be atypical. We present three immunocompromised pediatric patients with S. maltophilia infections. All three cases were fatal. We hope our experience at MD Anderson can guide providers to diagnose and properly treat Stenotrophomonas infection, as timely treatment may improve morbidity and mortality.