Although the functional and clinical significance of the stemness signature, including components of the Hh and PcG pathways, remain to be elucidated, we suggest that BMI1 expression along with Gli-1-positive expression is a link between relapse and CRT-resistant cancer cells, and is thus a potential prognostic biomarker and rational therapeutic target for attacking the ‘more aggressive’ cancer cells causing recurrence and treatment resistance. The gene discussed is GLI1; the disease is cancer.