A 12-year-old girl from Zaire with AIDS (CDC: P2 D1) presented with a generalized molluscum contagiosum infection. She had suffered from systemic cryptococcosis and from cryptosporidiosis several months before admission. While molluscum contagiousum infection is usually a self-limiting disease in immunocompetent persons, a fulminant appearance and persistence of giant mollusca occurs with advanced immunodeficiency. Histological and immunohistological examinations showed a severe diminution of Langerhans and T cell populations that might enhance the dissemination of the infection. Molluscum-like lesions of cryptococci have been described, and cutaneous cryptococcosis is the main condition to be considered in the differential diagnosis. Further differential diagnoses should include American and African histoplasmosis, and the cutaneous manifestations of mycobacterial infections, of toxoplasmosis and of Pneumocystis carinii infection.