 Liver cancer is the third leading cause of cancer death worldwide. Despite efforts to prevent and treat liver cancer, its incidence continues to rise. One promising lead researchers are pursuing is the role of hyperpolyploidy, a condition where cells end up with an abnormal number of chromosomes. While not uncommon in healthy liver cells, hyperpolyploidy could point to new targets in the fight against cancer. In a recent study in mice, researchers found that exposure to genotoxins, substances that cause DNA damage, led to the formation of hyperpolyploidy hepatocytes. This occurred due to the failure of liver cells to complete the final step of cell division, where two daughter cells physically separate from one another. The result was a subset of cells with abnormal numbers of copies of DNA. In experiments, these hyperpolyploid cells were found to give rise to preneoplastic lesions, early signs of cancer development. Interestingly, the team discovered that the process of reversing polyploidy, where the DNA content of cells is reduced, was a critical step in turning hyperpolyploid hepatocytes into cancer cells. These findings offer new insights into the role of genome content switching in the biology of liver cancer. But perhaps more importantly, they identify hyperpolyploidy as a potential biomarker for the early diagnosis and prevention of liver cancer. The researchers aimed to use advanced fingerprinting techniques, from visium spatial gene expression to transcriptomics, proteomics, and metabolomics to study the markers and signaling pathways that control hyperpolyploidy in liver cells. By analyzing gene expression patterns and small molecules present in blood samples, they hope to identify specific markers associated with the development and progression of liver cancer. Combining these results with maps of gene expression across the liver will provide an idea of how different cell types and states contribute to the formation of tumor cells and how they interact spatially. These research efforts have the potential to make a significant impact on liver cancer biology and improve clinical strategies for managing this deadly disease.