Hells deficiency in retinal progenitor cells did not affect the overall development of retina; however, genetic disruption of Hells in Rb1/Rbl1‐double knockout mice led to a significant decrease in RB development with delayed tumor progression, supporting the notion that lack of timely transcriptional repression of Hells during retinal development owing to the loss of Rb family genes significantly contributes to RB tumorigenesis. Here, HELLS is linked to neoplasm.