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Abstract Labial necrosis is a rare condition with diverse causes, posing challenges for diagnosis and treatment. Methicillin‐resistant Staphylococcus aureus (MRSA) strains, particularly those positive for Panton‐Valentine leukocidin (PVL), further complicate management due to antibiotic resistance and heightened virulence. We present three cases of labial necrosis caused by MRSA, two of which resulted positive for PVL. The first case involved a 35‐year‐old male with persistent lip edema and inflammation, which progressed despite various treatments. MRSA was isolated, and the patient responded to daptomycin and clindamycin therapy. The second case featured a 38‐year‐old male with intense lip pain and swelling, initially misdiagnosed as angioedema. The patient improved after treatment with daptomycin and clindamycin, along with nasal decolonization. The third case involved a 19‐year‐old male with rapid upper lip swelling following manipulation of a boil. Prompt drainage and antibiotic treatment led to complete resolution. These cases underscore the importance of considering MRSA and PVL‐positive S. aureus as potential etiologies in labial necrosis, especially in young individuals without underlying medical conditions. Effective management involves incision and drainage, complemented by antibiotic therapy tailored to drug resistance and virulence factors.