Abstract Background Cervical and prostate cancers have an important burden of disease, especially in developing countries. Self-efficacy for requesting screening is a key element in prevention activities. In this study we compared self-efficacy for requesting screening among Colombian females and males, to explore potential joint factors associated with both sexes. Methods A mixed study with development design was realized with 50 females and 50 males. First sociodemographic, medical data, and the cancer screening self-efficacy scale (original and ad hoc scale for males) were collected among participants. They were classified according to levels of self-efficacy and their risk factors were identified with robust regression. Semi-structured interviews with individuals with specific characteristics were realized to ascertain with detail about explanations for differences in requesting screening. Elements of the health belief model were the categories analyzed. Results Females and males were similar except in religion, occupation, and antecedents of Pap or rectal examination. Self-efficacy for requesting screening was higher among females (adj. β: -15.29, 95% CI:-18.36 to -12.21) and non-believers (adj. β: -5.38, 95% CI: -10.33 to -0.44). 27 individuals (18 males and 9 females) with low and high self-efficacy, and non-believers (atheists) were selected for interviews. Participants suggested that females are more susceptible than males because men need to feel symptoms. Shame and discomfort are barriers expressed by both sexes. Machismo is a strong barrier to request screening. Religion associate sex with impurity and it is a barrier among females. Health care services only focus on female screening. Conclusions Gender roles and religion (Catholicism and other Christian) elements are cultural expressions that determine the request of cancer screening. Further interventions should consider cultural elements to improve screening coverage. Key messages There are important sex differences in requesting cervical or prostate cancer screening. Culture (gender roles and religion) expressions determine cancer screening.