Lipoatrophia semicircularis, a rare entity which presents as atrophic cutaneous indentations exclusively on the anterior thighs of women, is thought to result from physical trauma. Localized lipoatrophies are common following injection with drugs and occur in patients with collagen disease. We report a 10-year-old girl who developed semicircular lipoatrophy on the anterior thighs after treatment of systemic lupus erythematosus (SLE) with subcutaneous injections of methotrexate. Until now, subcutaneously administered methotrexate has not been reported to cause lipoatrophy. Other possible causes include underlying autoimmune disease, the predisposition for females to be affected, and local trauma, also from the injections, at the specific body site. We suggest that subcutaneous injections with methotrexate on the anterior thighs should be avoided or monitored closely in female patients with SLE.