Tamoxifen is widely used in the treatment of breast cancer and associated with an increased risk of thromboembolism (TE). An elevated homocysteine is one of the risk factors for TE. The aim of the study was to assess the effect of tamoxifen on serum homocysteine levels in breast cancer patients. We performed a case-control study in 20 female subjects to evaluate the relationship between homocysteine levels, and 5,10-methylenetetrahyrofolate reductase (MTHFR) C677T and dihydrofolate reductase (DHFR) 19-bp intron-1 deletion polymorphisms in breast cancer patients and in control subjects. It was observed that homocysteine levels were decreased during tamoxifen therapy, but this finding was not statistically significant. There was also no statistically significant difference in homocysteine levels between the two groups (p> 0.05). MTHFR C677T and DHFR 19-bp deletion polymorphisms were not associated with serum homocysteine value in either group.