BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an unrecognized infection in non-HIV patients, particularly those with solid and hematologic malignancies. These patients experience higher mortality rates. This study aims to describe the incidence, initial characteristics, management, and outcomes of PCP at a tertiary cancer care center. METHODS: This retrospective observational study included all patients who underwent P. jirovecii PCR testing at our center from January 2019 to January 2022. PCP was diagnosed in PCR-positive patients. Data on demographics, treatment, and outcomes were extracted from medical records. The primary outcomes were ICU admission and 21-day mortality. Statistical analysis compared PCR-positive and PCR-negative patients, with a specific focus on lung cancer patients, and analyzed determinants of 21-day mortality in PCP patients. RESULTS: Of the 345 patients suspected of PCP, 54 (15.7%) were diagnosed with PCP. PCP patients were generally older. None of the PCP patients were on prophylaxis, compared to 14.8% of PCR-negative patients. In lung cancer patients, age and radiotherapy within the past year were significantly associated with a PCP diagnosis. The 21-day mortality rate among PCP patients was 35.4%. Independent risk factors for mortality included age and hematologic malignancy, while recent chemotherapy and higher neutrophil counts were associated with lower mortality. CONCLUSION: PCP is associated with the highest mortality in patients with hematologic malignancies and lung cancer. The findings underscore the importance and efficacy of prophylaxis in at-risk groups and should raise awareness for the diagnosis of PCP in overlooked populations, such as older cancer patients and those undergoing radiotherapy.