Pneumomediastinum is a rare, potentially life-threatening complication of PCP that occurs in HIV-positive and HIV-negative patients. We are presenting a rare case pneumomediastinum caused by pneumocystis Jirovecii pneumonia in a HIV-negative patient with history of diffuse B-cell lymphoma on R CHOP chemotherapy. What is unique about our case is that the patient developed pneumomediastinum while in the hospital, on atovaquone that improved when switched to clindamycin and primaquine with improvement in her respiratory status. Another interesting point is that diagnosis was entertained due to the characteristic CT scan finding of ground glass opacities with cystic lung lesions and pneumomediastinum in an immunocompromised patient who was started on empirical treatment for PCP. The diagnosis was eventually confirmed with PCP PCR.