Although Notch has been previously implicated in breast cancer stem cell self-renewal (Harrison et al, 2010; McGowan et al, 2011; Sansone et al, 2007) the CD44+CD24neg T-ISC sub-population was unaffected by Notch inhibition in 2D culture, sphere and xenograft assays, revealing a heretofore unappreciated heterogeneity in GSI responsiveness in T-ISC. The gene discussed is CD44; the disease is breast cancer.