Decay-accelerating factor (DAF, CD55) is physiologically acting as an inhibitor of the complement system, but is also broadly expressed in malignant tumours. Here DAF seems to exert different functions beyond its immunological role such as e.g. promotion of tumorigenesis, decrease of complement mediated tumor cell lysis, autocrine loops for cell rescue and evasion of apoptosis, neoangiogenesis, invasiveness, cell motility, and metastasis via oncogenic tyrosine kinase pathways and specific seven-span transmembrane receptors (CD97) binding. Therefore, DAF has already become a target for therapy. In this paper we review the role of DAF in human malignancies as described in different basic, diagnostic and experimental therapeutic studies.