The invention is directed to a method of monitoring or detecting treatment-resistant clones in a patient being treated for a lymphoid or myeloid neoplasm from which patient-specific correlating clonotypes have been identified. In some embodiments, such method includes the steps of obtaining a sample from the patient comprising T-cells and/or B-cells; amplifying molecules of nucleic acid from the T-cells and/or B-cells of the sample, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; sequencing the amplified molecules of nucleic acid to form a clonotype profile; determining from the clonotype profile a level of each correlating clonotype and clonotypes clonally evolved therefrom; and correlating a presence of a treatment-resistant clone of the neoplasm with a change in relative levels of the correlating clonotypes and clonotypes clonally evolved therefrom. In part, the invention permits one to distinguish between cases where treatment is effective but insufficiently intense and cases where a cancer clone arises that is resistant to a current treatment approach.