Immunohistochemical expression of metallothioneins (MTs), a group of intracellular metal-binding proteins, is well documented in breast cancer. However, there is a paucity of information on the expression of the different MT isoforms in breast cancer tissues. The dichotomous association of MT overexpression with tumour types and progression led us to examine the role of the MT-1F mRNA isoform in breast cancer. We evaluated MT expression in 48 primary invasive ductal breast cancer tissues by immunohistochemistry, and the corresponding MT-1F mRNA expression via a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. The specificity of the RT-PCR products was confirmed by direct cycle sequencing and restriction enzyme digestion. Immunohistochemical analysis of MT revealed a significantly higher MT expression in histological grade 3 tumours as compared to grade 1 and 2 tumours (p = 0.021). Similarly, MT-1F mRNA expression was found to be significantly higher in grade 3 tumours (p < 0.001). The results suggest that the MT-1F isoform influences histological differentiation in invasive ductal breast cancer. The converse is also true in that the histological grade may determine the level of MT-1F expression in breast cancer.