A method for determining a genomic DNA methylation profile in a sample comprising: (a) obtaining a substantially purified test genomic DNA sample; (b) contacting a portion test genomic DNA of the sample with: a first reaction mixture comprising: (i) at least two methylation sensitive restriction endonucleases; (ii) a hot-start DNA polymerase; (iii) a pH buffered salt solution; (iv) dNTPs; (v) DNA primer pairs for polymerase chain reaction amplification of at least a first, second and third different genomic region in the DNA sample; and (vi) fluorescent probes complementary to sequences in said first, second and third different genomic regions for quantitative detection of amplified sequences from the first, second and third different genomic regions, wherein each of the probes comprises a distinct fluorescent label, wherein: the first genomic region is a cleavage control that is known to be unmethylated; the second genomic region is a copy number control that does not include any cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; and the third genomic region is a test region having an unknown amount of methylation and including at least three cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; (c) subjecting the first reaction mixture to digestion and thermal cycling, while detecting fluorescent signals from the fluorescent probes, thereby performing real time PCR on the samples in the first and second reaction mixtures; (d) using the detected fluorescent signals to determine the genomic DNA methylation profile in a sample. (a) obtaining a substantially purified test genomic DNA sample; (b) contacting a portion test genomic DNA of the sample with: a first reaction mixture comprising: (i) at least two methylation sensitive restriction endonucleases; (ii) a hot-start DNA polymerase; (iii) a pH buffered salt solution; (iv) dNTPs; (v) DNA primer pairs for polymerase chain reaction amplification of at least a first, second and third different genomic region in the DNA sample; and (vi) fluorescent probes complementary to sequences in said first, second and third different genomic regions for quantitative detection of amplified sequences from the first, second and third different genomic regions, wherein each of the probes comprises a distinct fluorescent label, wherein: the first genomic region is a cleavage control that is known to be unmethylated; the second genomic region is a copy number control that does not include any cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; and the third genomic region is a test region having an unknown amount of methylation and including at least three cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; the first genomic region is a cleavage control that is known to be unmethylated; the second genomic region is a copy number control that does not include any cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; and the third genomic region is a test region having an unknown amount of methylation and including at least three cut sites for the methylation sensitive restriction endonucleases of the first reaction mixture; (c) subjecting the first reaction mixture to digestion and thermal cycling, while detecting fluorescent signals from the fluorescent probes, thereby performing real time PCR on the samples in the first and second reaction mixtures; (d) using the detected fluorescent signals to determine the genomic DNA methylation profile in a sample.