We investigated what factors may foster or hinder physicians’ cancer screening risk literacy–specifically the ability to understand evidence regarding screening effectiveness and make evidence-based recommendations to patients. In an experiment, physicians in training (interns and residents) read statistical information about outcomes from screening for cancer, and had to decide whether to recommend it to a patient. We manipulated the effectiveness of the screening (effective vs. ineffective at reducing mortality) and the demand of the patient to get screened (demand vs. no demand). We assessed participants’ comprehension of the presented evidence and recommendation to the patient, as well as a-priori screening beliefs (e.g., that screening is always a good choice), numeracy, science literacy, knowledge of screening statistics, statistical education, and demographics. Stronger positive a-priori screening beliefs, lower knowledge of screening statistics, and lower numeracy were related to worse comprehension of the evidence. Physicians recommended against the ineffective screening but only if they showed good comprehension of the evidence. Physicians’ recommendations were further based on the perceived benefits from screening but not on perceived harms, nor the patient’s demands. The current study demonstrates that comprehension of cancer screening statistics and the ability to infer the potential benefits for patients are essential for evidence-based recommendations. However, strong beliefs in favor of screening fostered by promotion campaigns may influence how physicians evaluate evidence about specific screenings. Fostering physician numeracy skills could help counteract such biases and provide evidence-based recommendations to patients.