This report describes four skin-puncture accidents with needles that were heavily contaminated with Cryptococcus neoformans. In one accident, delayed administration of antifungal drugs resulted in a granuloma of the finger. In the other three accidents, no skin infection followed immediate prophylaxis with oral fluconazole. Our experience suggests that early therapy with fluconazole is a reasonable means of managing skin injuries caused by instruments contaminated with viable C. neoformans.