The present invention relates to a new medical use of fenretinide or bioactive derivatives thereof, particularly to the use of fenretinide or bioactive derivatives thereof in the preparation of a medicament for eliminating or killing tumor stem cells in a subject or for treating and/or preventing a tumor disease originating from tumor stem cells in a subject. The invention further relates to a new use of fenretinide or bioactive derivatives thereof in combination with other anti-tumor agents, a pharmaceutical composition comprising said fenretinide or bioactive derivatives thereof and at least one additional anti-tumor agent, a method of screening said other anti-tumor agent, a method of eliminating or killing tumor stem cells or particularly hematologic tumor stem cells in a subject by administrating said fenretinide or bioactive derivatives thereof, as well as a method of eliminating or killing tumor stem cells and tumor cells derived from tumor stem cells, particularly hematologic tumor stem cells and hematologic tumor cells derived from hematologic tumor stem cells in a subject by administrating said fenretinide or bioactive derivatives thereof in combination with other anti-tumor agent(s).