The incidence of early-onset colorectal cancer (EO-CRC) is surging, and by 2030, one-third of all CRCs will occur before the commonly recommended screening age of 50 years. The time required for EO-CRC to reach the metastatic stage is unknown, yet this knowledge is critical to tailor early-diagnosis screening strategies. Here, Mauri, Patelli, et al. discuss how defining a key biological feature of EO-CRC may be central to protecting young adults from an alarming and probably unprecedented tumor epidemic.