Hereditary breast and ovarian cancers are autosomal dominant diseases frequently caused by mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2). BRCA1/2 are DNA repair genes, and their protein products regulate homologous recombination (HR). While deficient HR is a trigger for tumorigenesis, it also represents an Achilles heel that can be targeted during cancer treatments. In such a notion, BRCA1/2-deficient cancer cells are highly sensitive to poly-ADP-ribose polymerase inhibitors (PARPi) due to the trapping of PARP on DNA. The persistence of those adducts augments double-strand break formation, which is selectively toxic in BRCA1/2-deficient cells without affecting the normal cells of patients. Such a phenomenon of increased lethality due to the genetic context is defined as “synthetic lethality” (SL). However, probably following the high genomic instability that these drugs propitiate, resistance to PARPi has been repeatedly reported in the clinic, so other therapeutic alternatives are necessary. Previous data obtained by our team indicate that a deficiency in BRCA1/2 could generate an exacerbated dependency on regulators of the M phase. Based on these, this project aimed to identify molecular targets with already characterized pharmacological inhibitors, which may directly or indirectly modulate the M phase, and which also induce SL in BRCA1/2 deficient contexts to identify alternative conditions to PARPi. Five of the nine mitotic inhibitors evaluated caused SL in only one of the two genetic contexts (BRCA2 and not BRCA1). This could suggest a mechanism of action different from the one of PARPi. Supporting this hypothesis, some of these mitotic inhibitors did not show signs of replicative stress or genomic instability. In conclusion, our results contribute to the identification of possible novel pharmacological targets that could provide therapeutic alternatives for the treatment of tumors with BRCA2 deficiency.