- Background: Although several studies have demonstrated a possible relationship between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia and several solid tumors, it is still debatable whether SLE patients have an increased incidence of cancer overall. Case: We describe a 25-year-old patient with SLE who developed invasive squamous cell carcinoma of the vulva. The patient underwent radical vulvectomy and bilateral groin sentinel lymph node dissection and until to date, one year after surgery, she is alive without evidence of recurrent disease. Conclusions: Only three cases of vaginal/vulvar cancer associated with SLE have previously been mentioned in the literature, but not described in detail. This is the first detailed case report in the literature of vulvar invasive squamous cell carcinoma occurring in a SLE patient. It can only be speculated that the SLE itself and/or the treatment with immunosuppressive drugs provoked malignant transformation and the development of vulvar squamous cell carcinoma in such a young patient.