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INTRODUCTION: Osimertinib is a molecular targeted antineoplastic tyrosine kinase inhibitor that is primarily used in the treatment of non-small cell lung cancer (NSCLC). It has been associated with the development of interstitial lung disease/pneumonitis that requires discontinuation of the drug and occurs usually within the first 2-3 months of therapy. Approximately 3% of patients treated with osimertinib will experience lung toxicity. Acute fibrinous and organizing pneumonia (AFOP) is a rare form of interstitial pneumonitis that has been associated with drug toxicity but to our knowledge has not yet been described in association with osimertinib. Here we present one such case. DESCRIPTION: A 77 year old woman with a history of EGFR+ stage IIB adenocarcinoma presented with two weeks of shortness of breath, fevers, and dry cough. She had been started on osimertinib two months prior to presentation. On admission she was noted to be hypoxic with new oxygen requirement of 4L nasal cannula. CT chest showed bilateral ground glass opacities. She was started on empiric vancomycin and zosyn without improvement in symptoms. She underwent bronchoscopy on hospital day 3 with lung biopsy pathology showing AFOP. Infectious workup including bronchoalveolar lavage, blood, and sputum cultures, as well as respiratory viral panel and COVID-19 test was negative. Transthoracic echocardiogram showed normal cardiac function with an ejection fraction of 64%. Given these findings she was started on methylprednisolone 1 mg/kg for TKI-induced pneumonitis on day 5. Her oxygen requirements increased during hospitalization and on day 7 she acutely desaturated and was intubated. Repeat chest CT was negative for pulmonary embolism but showed interval worsening of infiltrates and consolidation at lung bases. Her methylprednisolone was increased to 2 mg/kg on day 10. Her pulmonary function improved and she was extubated to nasal cannula on day 12. DISCUSSION: Molecular targeted antineoplastic agents have been associated with lung toxicity, which can be severe and even fatal. To our knowledge this is the first known case of osimertinib-induced AFOP, which improved with discontinuation of the drug and initiation of high-dose methylprednisolone.