Clostridioides difficile (C. difficile) is an important nosocomial infection that is commonly associated with antibiotic use with pseudomembranous colitis being present in only 13% of cases. Disease severity ranges from asymptomatic carriers to severe complicated disease, based on clinical and laboratory findings. There is no single rapid FDA-approved test to diagnose C. difficile infections (CDI) and diagnosis usually requires a multi-step diagnostic approach. C. difficile testing usually begins with the C. difficile toxin and glutamate dehydrogenase antigen screen (GDH). If testing is negative for either, then nucleic acid amplification testing (NAAT) is done to confirm the diagnosis. Endoscopic evaluation may be required in rare instances when there is a high clinical suspicion of disease with negative testing. Here, we present an interesting case of a patient with multiple negative C. difficile toxin and GDH tests. Given the high index of clinical suspicion of CDI, the patient underwent a colonoscopy which revealed diffuse pseudomembranous colitis. The patient was then appropriately treated with oral vancomycin. We aim to shed light on the different testing modalities available to clinicians and the indications for doing a colonoscopy to delineate between false positive testing and active CDI.