Disclosed herein are methods of detecting presence of a gene fusion in a sample from a subject. In some embodiments, the methods of detecting presence of a fusion gene in a sample from a subject utilize a fusion probe that spans the point of fusion between two nucleic acids or genes, and detecting the fusion probe after nuclease treatment. In other embodiments, the methods of detecting presence of a fusion gene in a sample from a subject utilize two or more probes that flank the point of fusion between two nucleic acids or genes, and detecting these probes after nuclease treatment. In additional embodiments, the methods can include determining the percentage of gene fusion in the sample relative to the first nucleic acid or the second nucleic acid.