CASE PRESENTATION: A 71-year-old female with Stage IIA invasive lobular carcinoma breast cancer (cT2N0; estrogen, progesterone and HER-2/neu positive) was treated with six courses of docetaxel, carboplatin, pertuzumab and trastuzumab without complication. She was then started on trastuzumab monotherapy and three weeks later, she developed acute hypoxemic respiratory failure with ARDS. Trastuzumab was stopped with no improvement. She was empirically treated with broad-spectrum antibiotics (including empiric Pneumocystis treatment) and antifungal, as she was too unstable for safe bronchoscopy. Having no improvement, she was treated with pulse steroids but failed to respond and died five weeks after presenting with ARDS. Autopsy showed diffuse alveolar damage and organizing pneumonia with negative cultures.