Sigma (σ) receptors have been implicated in cancer. However, to date there is little molecular data demonstrating the role of σ1 receptors in cancer. Expression of σ1 receptors in various human cancer cell lines in comparison to non-cancerous cell lines was investigated, using real time RT-PCR and by western blotting with a σ1 receptor specific antibody. Our results indicate that cancer cells express higher levels of σ1 receptors than corresponding non-cancerous cells. Localization of the σ1 receptor was investigated in MDA-MB-231 cells by immunocytochemistry and confocal microscopy, expression was visualized predominantly at the cell periphery. We have tested the effect of σ1 and σ2 drugs and a σ1 receptor silencing construct on various aspects of the metastatic process on two breast cell lines of different metastatic potential and a normal breast cell line. Both σ1 and σ2 drugs and the σ1 receptor silencing construct had effects on proliferation and adhesion for breast cancer cell lines, compared to a non-cancerous breast cell line. This data suggests σ1 receptor plays a role in proliferation and adhesion of breast cancer cells. Therefore, it is likely to be a potential target for the diagnosis and therapy of breast cancer.