Schwartz CJ, Dolgalev I, Vasudevaraja V, et al. - Laser capture microdissection coupled with whole-exome sequencing to examine clonal origin in multifocal breast cancer (MFBC) was used to enhance the understanding of MFBC pathogenesis. Three cases of intramammary/intralymphatic spread from a single index tumor (MBC-1) (C1 to C3) and multiple independent tumors with each focus carrying its corresponding ductal carcinoma in-situ (MBC-2) (C4 to C6) were chosen and assessed three foci from each case. When contrasted with MBC-2, MBC-1 cases were histologically comparable and exhibited a robust predilection for satellite foci, vascular invasion and nodal metastasis. This bioinformatics approach gave robust evidence for clonal associations in MBC-1, as shown by different clusters of genes conserved across all tumor foci. Conversely, across all the foci in MBC-2, no gene clusters were shared, implying various independent tumors. These findings give additional support for the two different pathogenetic mechanisms in MFBC.