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Cancer is among the top five causes of death worldwide and is considered a public health problem. Therefore, this study evaluated the cytotoxic effects of different extracts of Lafoensia pacariA. St.-Hil., Lythraceae, stem bark on tumor cells (MCF-7 and MDA-MB-231) to determine the most selective combination of solvent extracts and to assess uptake of components of these extracts into tumor and non-tumor (McCoy) cells. Extracts were produced using different solvents (water, methanol, acetone, and ethanol) in their pure forms or in mixtures. Chromatographic profiles to monitor cell uptake were obtained using LC-DAD-MS. The extracts were subjected to cytotoxicity and clonogenic assays and to chemometric studies to determine the main bioactive components. MDA-MB-231 cells were more sensitive than MCF-7 to L. pacariextracts. The selected extracts demonstrated anticlonogenic effects in both tumor lines at concentrations of 2 μg/ml and higher. The cytotoxic potential of the extracts was not attributed exclusively to ellagic acid, but to the mixture of compounds present. MDA-MB-231 captured and metabolized components of L. pacariextracts. This effect was not observed in normal cells. Methanol:ethanol resulted in L. pacariextracts with the greatest cytotoxic activity against breast cancer cells. Future studies are needed to investigate the mechanisms of action and internalization characteristics of these extract components.