The present disclosure relates to monoclonal antibodies anti-FGFR4 and their use as medicaments and diagnostic agents. In particular, it relates to an antibody which specifically binds to the acid box domain of FGFR4 and to specific portions thereof. Nucleic acids coding for said antibody, vectors and host cells for their expression and production, antibody-drug conjugates and pharmaceutical compositions comprising said antibody are also within the scope of the present disclosure. The present disclosure also relates to antibodies anti-FGFR4 for use for detecting, killing, affecting or inhibiting development and/or differentiation of colon cancer stem cells.