Studies on biomedical applications of nanoparticles are growing with a rapidpace. In medicine, nanoparticles may be the solution for multi-drug-resistance which is still a major drawback in chemotherapy of cancer. In the present study, we investigated the potential cytotoxic effect of silver nanoparticles (Ag NPs) and silver ions (Ag +) in both parent and tamoxifen-resistant T47D cells in presence and absence of tamoxifen. Ag NPs were synthesized (< 28 nm) and MTT assay was carried out. The associated IC 50 values were found to be: 6.31 ?g/ml for Ag NPs/parent cells, 37.06 ?g/ml for Ag NPs/tamoxifen-resistant cells, 33.06 ?g/ml for Ag +/parent cells and 10.10 ?g/ml for Ag +/resistant cells. As a separate experiment, the effect of subinhibitory concentrations of Ag NPs and Ag + on the proliferation of tamoxifen-resistant cells was evaluated at non-toxic concentrations of tamoxifen. Our results suggested that in noncytotoxic concentrations of silver nanomaterials and tamoxifen, the combinations of Ag +-tamoxifen and Ag NPs-tamoxifen are still cytotoxic. This finding may be of great potential benefit in chemotherapy of breast cancer; since much lower doses of tamoxifen may be needed to produce the same cytotoxic effect and side effects will be reduced. © 2010, Avicenna Journal of Medical Biotechnology. All rights reserved.