Cancer patients’ outcome and survival depends on the early diagnosis of malignant lesions. Several investigation methods used for the prevention and early detection strategies have specific limitations. More recently, epigenetic changes have been considered one of the most promising tools for the early diagnosis of cancer. Some of these epigenetic alterations including promoter hypermethylation of genes like P16INK4a, BRCA1, BRCA2, ERα and RARβ2, APC, and RASSF1A have been associated with early stages of mammary gland tumorigenesis and have been suggested to be included in the models that evaluate individual breast cancer risk. In lung cancer, P16INK4a and MGMT gene hypermethylation was observed in sputum years before clinical manifestation of the squamous cell carcinoma among smokers. Loss of GSTP1 function by DNA hypermethylation together with changes in the methylation levels of repetitive elements like LINE-1 and Sat2 was reported in prostatic preneoplastic lesions. Also, DNA hypermethylation for hMLH1 and MGMT DNA repair genes was reported in precursor lesions to colorectal cancer. These epigenetic alterations may be influenced by factors such as xenoestrogens, folate, and multivitamins. Detection of these changes may help determining cancer susceptibility and early diagnosis.