A method for identifying, in a sample that has been obtained, one or more target nucleic acid molecules differing from other nucleic acid molecules in the sample by one or more methylated residues, said method comprising: subjecting one or more target nucleic acid molecules in the sample to at least one methylation insensitive enzyme digestion reaction and at least one methylation sensitive enzyme digestion reaction to form a plurality of digestion products; denaturing the digestion products to form single-stranded digestion products; providing a plurality of oligonucleotide adapters, each oligonucleotide adapter comprising a first primer-specific portion and a 3' end, said 3' end configured to ligate to a 5' portion of a single-stranded digestion product and hybridized to its complement, wherein the complement of the 3' end is coupled to an oligonucleotide region that is complementary to a 5' portion of the single-stranded digestion product, said portion spanning across the methylation insensitive enzyme digestion sequence of the single-stranded digestion product; subjecting the digestion products to a ligation reaction comprising a hybridization treatment, wherein each of the single-stranded digestion products hybridize to their complementary region of the oligonucleotide adapter complement in a sequence-specific manner such that the 3' end of the adapter is adjacent to the 5'end of the single-stranded digestion product, and ligation treatment, wherein the 3' end of the oligonucleotide adapter ligates the 5' end of the adjacent single-stranded digestion product thereby forming adapter tagged digestion products; providing one or more primary oligonucleotide primer sets, each primary primer set comprising (i) a first primary oligonucleotide primer comprising a nucleotide sequence that is the same as the first primer specific portion of the adapter tagged digestion products and (ii) a second primary oligonucleotide primer comprising a nucleotide sequence that is complementary to a region of the digestion product that is 3' to one or more methylated, uncleaved restriction sites, and a second primer-specific portion; blending the plurality of adapter tagged digestion products, the one or more primary oligonucleotide primer sets, and a first polymerase to form a first polymerase chain reaction mixture; subjecting the first polymerase chain reaction mixture to one or more polymerase chain reaction cycles comprising a denaturation treatment, a hybridization treatment, and an extension treatment thereby forming primary extension products; and detecting and distinguishing the primary extension products, thereby identifying the presence of one or more target nucleic acid molecules differing from other nucleic acid molecules in the sample by one or more methylated residues. subjecting one or more target nucleic acid molecules in the sample to at least one methylation insensitive enzyme digestion reaction and at least one methylation sensitive enzyme digestion reaction to form a plurality of digestion products; denaturing the digestion products to form single-stranded digestion products; providing a plurality of oligonucleotide adapters, each oligonucleotide adapter comprising a first primer-specific portion and a 3' end, said 3' end configured to ligate to a 5' portion of a single-stranded digestion product and hybridized to its complement, wherein the complement of the 3' end is coupled to an oligonucleotide region that is complementary to a 5' portion of the single-stranded digestion product, said portion spanning across the methylation insensitive enzyme digestion sequence of the single-stranded digestion product; subjecting the digestion products to a ligation reaction comprising a hybridization treatment, wherein each of the single-stranded digestion products hybridize to their complementary region of the oligonucleotide adapter complement in a sequence-specific manner such that the 3' end of the adapter is adjacent to the 5'end of the single-stranded digestion product, and ligation treatment, wherein the 3' end of the oligonucleotide adapter ligates the 5' end of the adjacent single-stranded digestion product thereby forming adapter tagged digestion products; providing one or more primary oligonucleotide primer sets, each primary primer set comprising (i) a first primary oligonucleotide primer comprising a nucleotide sequence that is the same as the first primer specific portion of the adapter tagged digestion products and (ii) a second primary oligonucleotide primer comprising a nucleotide sequence that is complementary to a region of the digestion product that is 3' to one or more methylated, uncleaved restriction sites, and a second primer-specific portion; blending the plurality of adapter tagged digestion products, the one or more primary oligonucleotide primer sets, and a first polymerase to form a first polymerase chain reaction mixture; subjecting the first polymerase chain reaction mixture to one or more polymerase chain reaction cycles comprising a denaturation treatment, a hybridization treatment, and an extension treatment thereby forming primary extension products; and detecting and distinguishing the primary extension products, thereby identifying the presence of one or more target nucleic acid molecules differing from other nucleic acid molecules in the sample by one or more methylated residues.