Four patients were admitted to Columbia Presbyterian Medical Center for evaluation of lower extremity pain and swelling. Three patients were initially misdiagnosed with cellulitis and one patient underwent evaluation for dermatomyositis. After consultation by the dermatologist, a correct diagnosis of pyomyositis was made clinically and confirmed by imaging, surgery, or an interventional procedure. Wound, blood, and urine cultures were positive for methicillin-sensitive Staphylococcus aureus in 100%, 50%, and 25% of patients, respectively. After the appropriate diagnosis and treatment, all patients experienced rapid resolution of symptoms and a favorable outcome.