Background: Cancer is one of the foremost contributors to global disease bur den and constantly requires new therapeutic options. The development of new drugs has failed to keep up with its incidence. Hence, drug reprofiling strategies are emerging as novel therapeutic options. The study aimed to evaluate the anti-cancer activity of amodiaquine (anti-malarial drug) using a combination of murine and human breast cancer cell lines Methods: Amodiaquine was authenticated by ultra-violet spectrophotometry, high- performance liquid chromatography and 1D nuclear magnetic resonance. In vitro cytotoxicity of amodiaquine was evaluated against three breast cancer cell lines. MDA-MB-453, 4T1 and MDA-MB-231 cells were incubated with the drug at different concentrations (0.78, 1.56, 3.13, 6.25, 12.50, 25.00, 50.00, 100.00 μM) for 72 h, after which cell viability testing was conducted using the cell counting kit-8 assay. Negative control in which no drug was added to the cells was also evaluated. The flow cytometry analysis of MDA-MB-231 cells when treated with amodiaquine was also evaluated by a flow cytometer using annexin V/propidium iodide staining assay. Results: Cell viability studies showed that the IC50 values of amodiaquine on MDA-MB-453, 4T1, and MDAMB-231 cells were 6.48 ± 1.12, 10.50 ± 1.17, and 19.23 ± 1.16 μM, respectively. The flow cytometry analysis of MDA-MB-231 cancer cells treated with amodiaquine showed cancer cell death by necrosis. Conclusion: This study has shown that amodiaquine may be potentially reprofiled as an anti-cancer agent in managing androgen receptor-positive / HER-2 positive and triple-negative breast cancer types. An additional probable mechanism of action of anti-cancer activity of amodiaquine was found to be necrosis .