Human CYP1-CYP4 families play crucial roles in the biosynthesis, bioactivation, and detoxification of a diverse range of chemicals including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, and drugs. The same CYP isoform can be involved in the conversion of different substrates via both bioactivation and detoxification reactions depending on a substrate type. Furthermore, the same CYP isoform can convert the same substrate to different products depending on a tissue type. On the contrary, different CYP isoforms can convert the same substrate to a variety of products, either more toxic or less toxic than their parent compound. The metabolic diversity and dual character of biological effects dictate limited number of cancer types, in which CYPs are implicated. In our review, we highlight the latest advancements and current understanding of molecular mechanisms of the development of hormone-sensitive cancers tumors based on dysregulated CYP expression and mutagenic adduct formation. We discuss the variations in CYP activities including CYP gene polymorphisms, which affect interindividual differences in cancer and drug susceptibilities. We show that there is only limited data indicating the statistically significant association between CYP gene polymorphisms and cancer among different populations. The involvement of CYPs in anticancer drug metabolism associated with drug-drug interactions and drug resistance is also discussed.