Introduction: Spontaneous esophageal perforation (SEP) is a rare and potentially life-threatening condition usually caused by esophageal trauma due to instrumentation or prolonged vomiting and retching. SEP due to esophageal candidiasis (EC) is extremely rare. We present a case of SEP in a patient with EC despite treatment with systemic antifungals. Case Description/Methods: A 53-year-old woman with a history of stage IV lung adenocarcinoma treated with chemoradiotherapy and immunotherapy presented with fever, abdominal pain, diarrhea and hematochezia. Her symptoms were consistent with immune-checkpoint inhibitor colitis, similar to a recent episode that improved with corticosteroids. She has a history of radiation esophagitis in the form of superficial ulceration and stenosis affecting the proximal esophagus. High-dose intravenous corticosteroids were initiated. Due to minimal response, infliximab was administered. Colonoscopy was unremarkable and random biopsies were negative for cytomegalovirus (CMV). Upper endoscopy (EGD) revealed resolution of the initially seen ulceration and no evidence of stricture or stenosis. However, a new distal superficial esophageal CMV ulcer was found. CMV viral load was 6,810 IU/mL and was successfully treated with intravenous ganciclovir leading to viral clearance. EGD for ongoing hematochezia revealed severe esophageal candidiasis (EC) confirmed with histopathology (Figure 1). Despite completing a 14-day course of intravenous fluconazole was, she developed septic shock due to SEP leading to a hydropneumothorax (Figure 2 and 3). Pleural fluid culture was positive for C. albicans. At that stage, family decided to enroll her in home hospice where she died a few days later. Discussion: Although, EC is not uncommon in immunocompromised patients, it is usually treated successfully with antifungal agents in 80-90% of cases. Transmural invasive Candida infection, however, is exceptionally rare with only 4 confirmed cases in the literature. It may lead to esophageal perforation and esophageal-pleural fistula formation. A second-look EGD with culture and sensitivity is recommend in symptomatic patients with EC who fail to improve with treatment. However, there are no guidelines recommending a repeat EGD in immunocompromised patients who initially had minimal symptoms. Our case suggests that for those patients a repeat EGD should be done to ensure resolution of EC and discontinuation of immunosuppressive therapy should be considered.Figure 1.: Endoscopic picture showing mucosal yellow-white plaques throughout entire esophagus, consistent with candidiasis.Figure 2.: Non-enhanced CT (axial view) demonstrating right hydropneumothorax with loculated fluid components.Figure 3.: Esophagram with extravasation of contrast from superior upper esophagus extending into right upper chest.