A 53-year-old Chinese man presented with fever, a painful exudative plaque around his left eye and subsequent multiple tender plaques and nodules on his bilateral face, neck and back. He had a 12-year history of refractory anemia, a subtype of myelodysplastic syndrome. Repeated bacterial cultures of exudates from the lesion of the left zygomatic area showed growth of methicillin-resistant Staphylococcus epidermidis. A biopsy of a plaque on the back showed edema of the papillary dermis and marked neutrophilic infiltrates in the upper dermis. The patient was diagnosed with Sweet's syndrome (SS), and responded well to combination therapy of amoxycilline/sulbactam and corticosteroids. To our knowledge, this is the first reported case of SS associated with skin S. epidermidis infection.