Resistance to anoikis ("detachment-induced apoptosis") has been suggested to be a prerequisite for cancer cells to metastasize. In a functional screen for suppressors of anoikis, we identified the neurotrophic receptor TrkB. Upon s.c. inoculation in mice, TrkB-expressing cells formed highly invasive and metastatic tumors. Here, we discuss our findings within the context of the proposed role of TrkB in human malignancies and address the question of its feasibility as a target for cancer therapy.