Compatible with this model, the presented “checkerboard” model for cancer heterogeneity can be used to explain our findings in terms of variable cancer cell clone sizes, all spread more or less evenly across the tumor: the smallest “clones” or cancer cell areas with slightly varying ER pathway activity; small clones that have an active HH and/or TGFβ pathway, and possibly intermediate/large clones with varying PI3K pathway activity. The gene discussed is ESR1; the disease is cancer.