Collectively, we report that SAHA and 5-aza-dc either individually or in combination (i) modulate the expression of some epigenetic regulators i.e., DNMT1 and HDACs, (ii) increase the expression of ERα especially in ER-negative cells, and eventually (iii) sensitize breast cancer cells to TAM treatment. The gene discussed is ESR1; the disease is breast carcinoma.