Pharmacological interventions in depressed cancer patients entail the use of selective serotonin reuptake inhibitors (SSRIs), of which the most prescribed is fluoxetine. This compound has been shown to interfere with oestrogen-dependent gene transcription in vitro and also affect the proliferation of various cancer cells. Therefore, this study aimed to assess the capacity of fluoxetine and its main metabolite, norfluoxetine, to influence breast cancer proliferation in vitro, using the MCF-7 cell line. Both compounds exhibited anti-proliferative activity on MCF-7 cells, either alone or in combination with 17 beta-estradiol. However, norfluoxetine displayed weak co-proliferative effects at (sub)micromolar, biologically relevant concentrations.