BackgroundPrecision medicine in oncology aims to identify the most beneficial interventions based on a patient’s individual features and disease. However, disparities exist when providing cancer care to patients based on an individual’s sex.ObjectiveTo discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain.ResultsGenetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care.ConclusionsThe Sociedad Española de Oncología Médica created a Task Force group to raise oncologists’ awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably.