Laboratory evidence suggests that transfusion-related immunomodulation can be modified by blood management and storage practices, but it is likely of less intensity than the effect of the surgical stress response. Clinical evidence has questioned the independent effect of blood transfusion on cancer progression for some cancers but supported it for others. Despite major changes in surgery and anesthesia, cancer surgery remains a major player in perioperative blood product utilization. Prospective data is still required to strengthen or refute existing associations. Transfusion-related immunomodulation in cancer surgery is well-documented, but the extent to which it affects cancer progression is unclear. Associations between transfusion and cancer progression are disease-specific. Increasing evidence shows autologous blood transfusion may be safe in cancer surgery.