We report the case of drug-induced, acrolocalized Kaposi sarcoma (KS), arising multicentrically in both palms and soles of a male patient who has had widespread psoriasis since 12 years of age. This 59-year-old man, of Mediterranean origin, was HIV antibody-negative and had received oral prednisolone treatment over 5 months for chronic obstructive lung disease (initial dose: 75 mg/d). Eight months after discontinuing oral treatment the KS nodules regressed spontaneously and finally disappeared completely without additional treatment. Light and electron microscopic investigations confirmed the diagnosis of KS, whereas laboratory tests excluded HIV infection and suggested mild immune dysfunction. The existence of HLA loci predisposing to KS and to psoriasis (A1, DR5, DR7, DR11) was characteristic for the simultaneous occurrence of these two diseases. This case report demonstrates the complex interrelationships between genetic predisposition, drugs leading to immune suppression, and the evolution of an unusual neoplasm.