Iodine stimulates 1) ER-α mediated reporter transcriptional activity both in ER-positive and ER-negative but ER transfected breast cancer cells; 2) mRNA expression of ER-α regulated genes including PR, PS2, CyclinD1 and Cat-D; 3) protein expression of Cat-D, PR and CyclinD1; 4) an anchorage-dependent and –independent growth of ER-α positive breast cancer cells but not ER-α negative cells; and this stimulation is blocked by ER-α antagonist ICI 182,780; and 5) mRNA expression of CycinD1 and Cat-D in MCF-7 xenograft in ovariectomized mice by topical application of Iodine Tincture. This evidence concerns the gene ESR1 and breast cancer.