We report a 37-year-old female with signal transducer and activator of transcription 3 (<i>STAT3</i>)-deficient HIES, diffuse large B-cell lymphoma (DLBCL) in remission, rituximab-induced hypogammaglobulinemia, and recurrent infections, who presented with acute-on-chronic dyspnea. The gene discussed is STAT3; the disease is infection.