Introduction: Females with systemic lupus erythematosus (SLE) have higher prevalence of human papillomavirus (HPV) infection, which can lead to the development of warts. Herein we report the first case of giant disseminated condylomatosis (GDC) in a SLE female on mycophenolate mofetil (MMF). Case report: The patient, a 33-year-old, Black female, was diagnosed with SLE during her first pregnancy in 2003 based on the features of arthritis, skin rash, seizures, nephritis and presence of antinuclear antibodies. Her pregnancy resulted in preterm delivery of a stillborn fetus at 28 weeks. Since that time she has been treated with steroids and different regimens of immunosuppressive drugs such as cyclophosphamide, azathioprine and lately MMF. In the last few years she presented GDC involving the genital area in addition to skin on the lower abdomen. Topical therapy with trichloroacetic acid, imiquimod and podophyllin was only partially effective. Different types of HPV were identified in the lesions, being HPV-11 in abdomen, HPV 6, 11, 42 in vulva, HPV-6, 11 in vagina and HPV-6, 11 in endocervix. Conclusions: GDC may be a complication of SLE, secondary to the disease itself, its treatment or other factors not yet identified.