Studies indicate that smoking is significantly related to breast cancer mortality. One hypothesis is that this association is due to the elevated expression of proteins associated with resistance to cancer therapies. The metallothioneins (MTs) are a family of proteins that appear to play a role in conferring resistance to certain cancer therapies. This study was carried out to assess whether smoking was associated with MT expression in breast carcinomas. Archival breast tissues with accompanying clinical and epidemiological information were collected from three different cancer centers for 123 women diagnosed with invasive breast cancer. MT expression was assessed using immunohistochemical procedures and semi-quantified using an immunoreactivity score that was obtained by multiplying the percentage of MT-positive tumor cells by MT staining intensity. The results showed that 27.6% of the women were current smokers. Among women whose tissues were collected at the cancer center where enrolled women had primarily early stage, low grade breast cancer, smokers had increased odds, although not significantly, of having a MT-positive tumor compared to non-smokers, independent of cancer stage. This association was not observed among the women whose tissues were collected from the other cancer centers. These findings suggest that among specific groups of women, smoking at the time of breast cancer diagnosis may be associated with an increase in breast tissue MT.