Abstract Cancer is one of the leading causes of death and its prevalence increases with age. While centenarians exhibit extreme longevity and potential to avoid or delay aging-related diseases, their response to cancer is still barely explored. Our study took advantage of the Electronic Health Records to retrospectively compare the severity of cancer in centenarians (n = 649) and non-centenarians (n = 62,753) in the Basque Country (province of Gipuzkoa), Spain, through analyzing all the recorded diagnoses throughout their lifetime. Descriptive statistics were applied to discern differences between the two population groups in terms of prevalence of tumor types, number of diagnoses, and treatments. Survival analysis was performed through Kaplan–Meier estimator. We found that centenarians had fewer cancer diagnoses (17.1%, n = 111) than non-centenarians (40.5%, n = 25,405), and notably avoided the most aggressive cancer types and did not develop metastasis. Furthermore, they barely had records of treatments or drugs and had extended survival both since the first and last diagnosis of cancer. These results suggest resilience of the centenarians against malignant cancers explaining, in part, their extended longevity.