There is growing evidence that risk factors for cancer occurrence and for cancer death are not necessarily the same. Knowledge of cancer aggressiveness risk factors (CARF) may help in identifying subjects at high risk of developing a potentially deadly cancer (and not just any cancer). The availability of CARFs may have positive consequences for health policies, medical practice, and the search for biomarkers. For instance, cancer chemoprevention and cancer screening of subjects with CARFs would probably be more ethical and cost-effective than recommending chemoprevention and screening to entire segments of the population. Also, the harmful consequences of chemoprevention and of screening would be reduced while effectiveness would be optimised. We present examples of CARF already in use (e.g. mutations of the breast cancer (BRCA) gene), of promising avenues for the discovery of biomarkers thanks to the investigation of CARFs (e.g. breast radiological density and systemic inflammation), and of biomarkers commonly used that are not real CARFs (e.g. certain mammography images, prostate-specific antigen (PSA) concentration, nevus number).