An evolutionary perspective can help unify disparate observations and make testable predictions. We consider an evolutionary model in relation to two mechanistic frameworks of cancer biology: multistage carcinogenesis and the hallmarks of cancer. The multistage model predicts that cancer risk increases with body size and longevity; however, this is not observed across species (Peto's paradox), but the paradox is resolved by invoking the evolution of additional genetic mechanisms to suppress cancer in large, long-lived species.