Rothmann–Makai syndrome (lipogranulomatosis subcutanea) is a rare variant of Weber–Christian disease, but lacks visceral involvements and systemic manifestations. We herein report the case of a 56-year-old Chinese woman with this disorder who complained of subcutaneous tender nodules over her extremities, trunk, and face of 2 years' duration. She was firstly treated with 300 mg of oral roxythromycin for 8 weeks and subsequently treated with 400 mg of oral clarithromycin for the next 8 weeks. However, no significant effect was observed. She was then administered 200 mg of oral minocycline hydrochloride. After 1 week, her skin symptoms rapidly improved and no relapse has been observed in a follow-up period of 3 months. Considering that tetracycline antibiotics, but not macrolide antibiotics, inhibit the activity of pancreatic lipase in vitro, the efficiency of tetracycline antibiotics may be a clue to clarifying the pathogenesis of this disorder.