Epigenetic modifications have been reported in a number of non-germ-line tumor types. Epigenetic modifications to the genome, especially DNA methylation and histone modifications, affect gene expression causing increased risk for cancers and other diseases. We have summarized information about DNA methylation percentages in Glioblastoma multiforme (GBM) line HTB-12, alveolar cell carcinoma, and acute lymphocytic leukemia samples and determined H3 (K27) methyltransferase activity in GBM and leukemia cells and made comparisons to H3 (K27) methyltransferase activity in normal astrocyte, lung, and lymphocyte cells. GBM and alveolar cell carcinoma gDNA possessed lower gDNA methylation percentages compared to normal cells. Methyl-sensitive cut counting analysis (MSCC) showed fold decreases in GBM CpG methylation sites for genes PBK, KIF23, COL6A3, and LOX. There was no significant difference in CpG DNA methylation, but less histone methyltransferase activity in acute lymphocytic leukemia compared to normal cells. GBM possessed increased histone methyltransferase activity compared to normal samples. Challenges in the field in diagnosis and prognosis for cancer risk especially with regard to the results of this work are discussed.