Breast and cervical cancer are the first and fourth cancer types with the highest prevalence in women, respectively. The developmental profiles of cancer in women can vary by genetic markers and cellular events. In turn, age and lifestyle influence in the cellular response and also on the cancer progression and relapse. The human DEK protein, a histone chaperone, belongs to a specific subclass of chromatin topology modulators, being involved in the regulation of DNA-dependent processes. These epigenetic mechanisms have dynamic and reversible nature, have been proposed as targets for different treatment approaches, especially in tumor therapy. The expression patterns of DEK vary between healthy and cancer cells. High expression of DEK is associated with poor prognosis in many cancer types, suggesting that DEK takes part in oncogenic activities via different molecular pathways, including inhibition of senescence and apoptosis. The focus of this review was to highlight the role of the DEK protein in these two female cancers.