INTRODUCTION: Targeted cancer therapies have led to improvement in survival time and quality of life for patients with various cancer types, including advanced breast cancer. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for use in combination with exemestane for advanced hormone-receptor positive, HER2-negative breast cancer in post-menopausal women. While typically well-tolerated, a few cases of upper gastrointestinal bleeding from gastric antral vascular ectasia (GAVE) associated with everolimus have been described, primarily in oncology literature. In our patient, we present a case of gastrointestinal bleeding due to GAVE during treatment with everolimus. Given the clinical consequences of this adverse effect, gastroenterologists must maintain awareness of the associated risk of gastrointestinal hemorrhage and approach to treatment in patients treated with this agent. CASE DESCRIPTION/METHODS: Our patient is a 64-year-old female with stage III left breast invasive ductal carcinoma (HER2-negative, estrogen receptor positive, progesterone receptor positive). She underwent left lumpectomy, adjuvant doxorubicin and cyclophosphamide, paclitaxel, and radiation. Follow-up revealed bony metastases and right upper lobe pulmonary metastatic disease. She was initiated on exemestane and everolimus. Three weeks later, she presented with severe weakness and dyspnea. Rectal examination with dark hemoccult positive stools. Laboratory findings revealed Hgb of 6.0 g/dL. An upper endoscopy showed no source of bleeding. The patient responded to blood transfusions and Hgb stabilized. One month later, the patient represented with symptomatic anemia. A repeat upper endoscopy revealed blood with diffuse gastric antral oozing consistent with GAVE. She was treated with argon plasma coagulation (APC), and everolimus was discontinued. The patient stabilized after endoscopic therapy and was discharged after recovery. DISCUSSION: Gastrointestinal bleeding due to GAVE while undergoing treatment with everolimus is an uncommon event with an unknown mechanism. Review of current literature shows that few similar cases have been previously reported. Our patient responded well to therapy with APC. However, progression to life-threatening bleeding with poor response to endoscopic therapy has been described. As use of everolimus increases, we are more likely to encounter gastrointestinal bleeding due to GAVE. Clinicians should remain alert to the risk of severe bleeding and the utility of APC in these patients.