We have recently reported that the ferrocenyl diphenol compound 1,1-di(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene 1 exhibited strong in vitro anti-proliferative effects on both hormone dependent (MCF7, IC 50 = 0.7 μM) and hormone independent (MDA-MB231, IC 50 = 0.6 μM) breast cancer cells. In order to assess the importance of the ferrocenyl motif, we have prepared a series of analogs using the organometallic fragments (η 5-C 5H 4)Cp ∗Fe ( 7), ((η 5-C 5H 4)(CH 3) 2phospholyl)Fe ( 9), (η 5-C 5H 4)CpRu ( 10), (η 5-C 5H 4)Re(CO) 3 ( 11), and (η 5-C 5H 4)Mn(CO) 3 ( 12), and the chlorinated ferrocenyl derivative 1,1-di(4-hydroxyphenyl)-2-ferrocenyl-4-chloro-but-1-ene ( 4). The nature of the organometallic moiety had a strong influence on estrogen receptor alpha (ERα) recognition, with relative binding affinity (RBA) values ranging from 0.55% to 10.8%. The second isoform of the estrogen receptor, ERβ, was better able to accommodate these compounds, with RBA values ranging from 8.9% to 17.1%. Molecular modeling studies suggest that the orientation of the compounds and their interactions with the residues of ERα and ERβ binding sites are very similar. A study on the MCF7 hormone dependent breast cancer cell line revealed an anti-proliferative effect for the ferrocenyl phenols 1 and 4, while the other compounds displayed either a proliferative effect ( 9– 12), or no effect ( 7). The anti-proliferative effect of 1 and 4 is also evident in the MDA-MB231 hormone independent breast cancer cell line (IC 50( 4) = 1 μM), and can be attributed to the cytotoxicity of these compounds, while the other compounds showed no effect on this cell line. The cytotoxicity of 1 and 4 may arise from electron delocalization in the radical cation in alkaline conditions, possibly resulting in a cytotoxic quinone methide formation, while the other complexes do not undergo the formation of this entity, as evidenced by the electrochemical results.