Background: Epidermal inclusion cysts (EIC) are one of the most common forms of cysts found on and/or underneath the skin. Inflamed EICs typically show signs and symptoms such as pain and erythema, mimicking cutaneous abscess. However, prior studies have demonstrated at least 20% of lesions are culture negative. Objective: To determine the rate of culture positivity in mild inflamed epidermal inclusion cysts, in particular to identify whether empiric antibiotics are warranted. Methods: In a retrospective chart review 76 cases of inflamed EIC that were mild (lacking systemic symptoms) were analyzed who presented to the department of dermatology at Mount Sinai between 2016-2019. Results: Of cultures taken from inflamed cysts, 47% resulted in no bacterial growth or growth of normal flora, 38.4% resulted in growth of aerobic bacteria with methicillin-resistant Staphylococcus aureus (8%), Staphylococcus lugdunensis (5%), and methicillinsensitive Staphylococcus aureus (13%) predominating, and 9.3% resulting in growth of anaerobic bacteria with Finegoldia magna, Peptostreptococcus, and Cutibacterium acnes presenting. Review of prescribed treatment regimens often involved antibiotic medication, despite a high prevalence of negative culture. Conclusions: Almost half of cases of mild inflamed EIC (lacking systemic symptoms) cultured will not grow pathogenic bacteria, therefore incision and drainage with culture and appropriate therapy is a viable therapeutic option in uncomplicated inflamed EIC lesions. In this way, over prescription of antibiotics can be minimized.