In patients presenting with classic signs and symptoms of cholecystitis, the diagnosis is made based on confirmatory imaging studies. However, the most commonly utilized imaging studies lack accuracy, especially in the case of acalculous disease. Here we discuss four cases of patients presenting with symptoms of cholecystitis. All four patients underwent multiple imaging studies, which yielded negative results. Due to persistent symptoms, the decision was made to proceed with cholecystectomy. Each patient underwent uncomplicated cholecystectomy, with resolution of symptoms post-operatively, and continued symptoms relief 6-10 months post-operatively. Cholecystitis is a clinical diagnosis. Negative imaging studies should not influence the management in a patient presenting with classic signs and symptoms of cholecystitis.