A variety of different point mutations in NTRK1, NTRK2, and NTRK3 were identified in biopsy samples from a subjects having a variety of different cancers. Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment including a therapeutically effective amount of a Trk inhibitor for a subject, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having a cancer, methods of determining a subject's risk for developing a cancer, and methods of assisting in the diagnosis of cancer that are based on the identification of a subject having a cell that has at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3, or the determination that a subject has a cell that has at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3. Also provided are kits that allow for the detection of at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3.