Chemo-　and　radiation　therapy　are　the　main　modalities　for　cancer　treatment.　A　major　limiting　factor　is　their　toxicity　to　normal　tissue,　thus　reducing　the　dose　and　duration　of　the　therapy.　The　hair　follicle,　gastrointestinal　tract,　and　hematopoietic　system　are　among　the　target　organs　that　often　show　side　effects　in　cancer　therapy.　Although　these　organs　are　highly　mitotic　in　common,　the　molecular　mechanism　of　the　damage　remains　unclear.　The　feather　follicle　is　a　fast-growing　mini-organ,　which　allows　observation　and　manipulation　on　each　follicle　individually.　As　a　model　system,　the　feather　follicle　is　advantageous　because　of　the　following　reasons:　(1)　its　complex　structure　is　regulated　by　a　set　of　evolutionarily　conserved　molecular　pathways,　thus　facilitating　the　effort　to　dissect　the　specific　signaling　events　involved;　(2)　its　morphology　allows　the　continuity　of　normal–perturbed–normal　structure　in　a　single　feather,　thus　“recording”　the　damaging　effect　of　chemo-　and　radiation　therapy;　(3)　further　histological　and　molecular　analysis　of　the　damage　response　can　be　performed　on　each　plucked　feather;　thus,　it　is　not　necessary　to　sacrifice　the　experimental　animal.　Here,　we　describe　methods　of　applying　the　feather　model　to　study　the　molecular　mechanism　of　chemo-　and　radiation　therapy-induced　tissue　damage.　©　Springer　Science+Business　Media　LLC　2017.