INTRODUCTION: Esophagogastroduodenoscopy (EGD) is a commonly performed diagnostic and therapeutic procedure with a low risk of adverse events, which can include cardiopulmonary events, hemorrhage, infection and perforation. Perforation can occur at the esophagus, stomach or duodenum, leading to pneumoperitoneum. However, what follows is a unique case of a patient who suffered a colonic perforation and pneumothorax after undergoing EGD. CASE DESCRIPTION/METHODS: A 71-year-old male presented with a 4-month history of epigastric pain, nausea and weight loss. His medical history was notable for coronary artery disease, hypertension, and chronic obstructive pulmonary disease. On exam, he exhibited epigastric tenderness without rebound, rigidity or guarding. CT scan showed wall thickening of the second portion of the duodenum. Magnetic resonance cholangiopancreatography showed biliary ductal dilatation without definitive obstructive lesion. EGD revealed pangastritis with nodular-appearing, edematous, and hyperemic gastric folds along with thickened duodenal folds, concerning for malignancy. At the completion of the procedure, the patient developed tachycardia and crepitus in his anterior chest wall extending into his neck. A flat plate indicated free intraperitoneal air. Repeat CT imaging discovered a large right-sided pneumothorax and a chest tube was placed. Exploratory laparotomy revealed extensive tumor burden within the mesentery of the large and small bowel with a perforation at the anterior portion of the transverse colon, which was resected with ostomy creation. Pathology was remarkable for invasive colon adenocarcinoma. DISCUSSION: While cases of large bowel perforation after colonoscopy are known, we found only one documented case following EGD involving a patient with pneumoperitoneum caused by a perforated sigmoid diverticulum. For our patient, pathology found that the malignancy had eroded through the lumen of the transverse colon. It is suspected that manipulation of the upper GI tract caused perforation of the transverse colon due to fibrosis in the mesentery and adhesions due to omental “caking” from extensive tumor burden. Since our patient’s injury occurred in the transverse colon, air from the perforation was able to travel to the mediastinum via fenestrations in the diaphragm which allowed air to enter the pleural space. Colonic perforation with pneumothorax is a rare complication after EGD and should be kept in mind by practitioners when the EGD shows friable tissue concerning for malignancy.