Background: Molluscum contagiosum (MC) is a frequent and usually benign cutaneous infection with molluscum contagiosum virus (MCV), affecting mainly children and young sexually active adults. With the emergence of HIV/AIDS, a new patient group at risk has been identified with often extensive skin involvement and recalcitrant disease.Main observations:We report a case of a girl with connatal HIV-infection, suffering from extensive, disseminated MC. Due to multi-resistance, an effective antiretroviral therapy could not be established for years, rendering an effective treatment of MC by established treatment options virtually impossible. An off-label use of imiquimod showed a marked improvement of lesion counts in this patient, whereas a complete clearance could only be achieved once effective antiretroviral therapy was introduced.Conclusions:We believe that imiquimod may represent a valuable treatment option for molluscum contagiosum especially in the context of marked immunosuppression, where sensitive areas like the face and neck are often involved and scarring must be avoided.