Roughly 50% of cancer cases occur in people aged 65 years or older. Older people are often diagnosed at a later stage and might receive less (intensive) treatment, which might affect the outcome. In addition, an older age might be associated with biological differences in tumour and microenvironment behaviour, a domain that has been poorly studied so far. In this narrative Review of published literature, we explored the reported differences in tumour biology according to age in five major cancer types: breast, colorectal, prostate, lung, and melanoma. Our literature search uncovered clear differences in tumour histology and subtype distribution in older people compared with younger patients, as well as age-specific patterns of tumour mutations and other molecular alterations. Several studies also indicate notable changes in tumour-infiltrating immune cells in tumours of older versus younger people, although this research is still in its infancy. More research is needed and might lead to a better understanding of the biology of ageing in relation to malignancy. This knowledge could provide new perspectives for more personalised cancer treatments, eventually improving the global outcomes of older patients with cancer.