A modelled analysis of two oncology units suggests that asymptomatic colonized patients drive the majority of transmission events that lead to new C. difficile colonizations. In surveillance data used to build and test the computational model, asymptomatic colonized individuals accounted for 92% of transmission events resulting in new colonizations. The findings challenge the common assumption that visibly sick patients are the main engine of spread in high-risk cancer wards. For infection prevention teams, it highlights where screening, isolation decisions, and operational interventions may need to be reweighted. Because C. difficile outbreaks can compound morbidity in immunocompromised populations, the study’s transmission-focused lens can influence future hospital protocols for cancer care settings.