Purpose Cancer is a disease of the elderly: 60 % of tumours occur in patients aged 65 years or older. Cancer-related fatigue is a common symptom experienced by cancer patients and cancer survivors that profoundly affects all aspects of the quality of life. Although it has been estimated that up to 70 % of elderly with cancer experience fatigue, this symptom is still largely ignored in ageing population. Methods We performed a systematic review of the literature identified by MEDLINE. Results The relationship between ageing process and pathogenesis of cancer-related fatigue is still not fully understood. Conclusions Ageing is associated with an increased prevalence of chronic diseases, decreased functional reserve in multiple organ systems and enhanced susceptibility to stress. Ageing and the concomitant presence of a condition of frailty may predispose to the presence of fatigue. Nevertheless, only few studies have to date specifically assessed the impact of fatigue in the geriatric population. Since cancer-related fatigue is a peculiarly debilitating condition characteristic of elderly cancer patient population, we suggest the early recognition and thorough evaluation of the symptom fatigue, its co-existing causes (i.e. anaemia, mood disorders and sleep disturbances) and co-morbidities (i.e., endocrine disorders, metabolic, cardiovascular and liver diseases).