Abstract: The objective of this study was to evaluate the impact of tamoxifen treatment on amount of fibroglandular tissue (FGT), background parenchymal enhancement (BPE), and cysts on breast MRI. Retrospective search identified 96 women with breast cancer who had a breast MRI both before and during adjuvant tamoxifen therapy between 2002 and 2008. After exclusion of all irradiated breasts, 88 women were eligible. Two readers blinded to tamoxifen treatment status independently rated level of BPE, amount of FGT, and cysts using a 4-point categorical scale: BPE––Minimal, Mild, Moderate, Marked; FGT––Fatty, Scattered, Heterogeneously Dense (HD), Dense; Cysts––Minimal, Mild, Moderate, Marked. A consensus interpretation was reached in cases of disagreement. During tamoxifen, there was a significant shift from higher to lower degree BPE, cysts, and FGT compared with before tamoxifen. BPE, cysts and FGT decreased in 68% (60/88), 38% (33/88), and 40% (35/88) of women during tamoxifen (p < 0.001 for all measures). After the exclusion of all cases with minimal BPE, cysts, or FGT on the pre-tamoxifen MRI, the percentage of women demonstrating a decrease in these factors increased to 81% (60/74), 77% (33/43), and 41% (35/86), respectively. Exclusion of patients treated with chemotherapy did not substantially change these results. The percentage of women with decreases in FGT and cysts increased with greater duration on tamoxifen, whereas decreases in BPE were detected early in treatment (<90 days) and did not change substantially with longer duration on tamoxifen. A significant association exists between treatment with tamoxifen and decreases in BPE, cysts, and FGT on breast MRI.