INTRODUCTION: Cetuximab is an epidermal growth factor receptor inhibitor that is used as part of metastatic colorectal cancer targeted therapy regimen. There are several known side effects of the drug caused by its mechanism of action. However, cetuximab is considered a liver-safe medication, and was only reported to cause mild transient elevation in liver transaminases, that is usually less than ten times the upper limit of the normal value. CASE DESCRIPTION/METHODS: A 23-year-old male, with a history of Lynch syndrome, recurrent squamous cell carcinoma of the tongue and oropharynx, and metastatic colorectal carcinoma. He was treated with cetuximab after progression of his metastatic colorectal carcinoma on FOLFOX chemotherapeutic regimen. The patient presented for percutaneous gastrostomy tube placement and was found to have a facial and truncal papulopustular rash and facial swelling. Laboratory workup (Figure 1A) revealed highly elevated liver enzymes with AST of 1624 IU/ml, ALT of 730 IU/ml, total bilirubin of 3.1 g/dl, direct bilirubin of 1.7 mg/dl and albumin of 3.6 g/dl. Further workup (Figure 1B) was unremarkable, and radiological imaging showed nonspecific findings. His liver profile continued to worsen during hospitalization (Figure 2) and the decision was to proceed with a liver biopsy. A liver biopsy showed acute hepatitis with severe mixed lobular inflammation and necrosis. Therefore, drug-induced liver injury was suspected. After careful review of the patient’s medication, cetuximab was stopped. On one-month follow up, overall improvement in liver profile ensued with an AST of 40 IU/ml, ALT of 32 IU/ml, total bilirubin 1.1 g/dl, direct bilirubin 0.4 mg/dl and albumin 3.5 g/dl. DISCUSSION: Our patient was treated with cetuximab to manage his metastatic carcinoma. The most common adverse reaction to the drug is skin toxicity, which is related to its mechanism of action. The patient developed a skin rash and liver toxicity. Drug-induced liver injury is an adverse drug reaction that is diagnosed by exclusion of other causes, and improvement upon withdrawal of the drug. We excluded other causes of liver disease including viral, autoimmune and other causes based on laboratory, radiologic and histopathologic findings. Liver profile improvement after the cessation of cetuximab confirms cetuximab induced liver injury. This is the first known documented case of cetuximab induced liver injury.Figure 1Figure 2