<p>Sex is a significant determinant of cancer incidence and outcome. The effects of sexual differentiation on normal and cancer biology underly this epidemiology. The resultant sex differences in therapeutic target pathways and processes provide a foundation for developing more personalized cancer treatments. However, our efforts at personalization cannot stop there. Humans also have gender, and sex and gender are highly interactive in individuation. Thus, we will also need to consider how gender–sex interactions (GSI) affect cancer biology and clinical parameters such as the timing of diagnoses, clinical trial enrolment, and the completeness of efficacy and toxicity data. Ignoring the effects of GSI can compromise the quality of basic biological and clinical data and the conclusions drawn from them. This is not to say that GSI will always have a significant effect or any effect at all in every cancer study. Rather, it is to say that we know enough about GSI and human cancer to anticipate measurable differences when GSI are considered in research, enabling us to experimentally determine whether their effects are significant. Here, I delve deeply into GSI and cancer, as this approach to treatment personalization holds great promise to benefit all patients with cancer.</p>