Liquid biopsy (LB) methods are continuously evolving. With marked shifts in sensitivity in recent years, LB has demonstrated utility in the discovery of novel biomarkers. In this issue, Xu and colleagues describe the use of the aqueous humor as a liquid biopsy for retinoblastoma, an intraocular tumor that forms in children. The cover depicts an artistic rendering that demonstrates a retinoblastoma genomic profile encircling an ocular photo of a large retinoblastoma tumor and active seeding of the vitreous humor of the eye. The genome demonstrates gain of chromosome 6p (red) which was shown in this study to be a prognostic biomarker indicating poor treatment response to melphalan and low likelihood of ocular survival. For more information, see the article on page 1166. Image credit & design: Liya Xu, Anand Kolatkar and Rafael Nevarez, Michelson Center for Convergent Biosciences, University of Southern California.