Objective: Quality of Life (QoL) in elderly cancer patients is a topic that has been little explored. This systematic review aims to identify, assess, and report the literature on QoL in home-dwelling cancer patients aged 80 years and older and what QoL instruments have been used. Methods: We systematically searched the databases of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsykINFO, Scopus, Epistemonikos and Cinahl to identify studies of any design measuring QoL among home-dwelling cancer patients aged 80 years and older. We screened the titles and abstracts according to a predefined set of inclusion criteria. Data were systematically extracted into a predesigned data charting form, and descriptively analyzed. The included studies were assessed according to the Critical Appraisal Skills Programme (CASP) checklists, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) checklist was used to ensure rigor in conducting our investigations and reporting our findings. This systematic review was registered in PROSPERO (CRD42021240170). Results: We included three studies that specifically analyze QoL outcomes in the subgroup of home-dwelling cancer patients aged 80 years and older, with a total of 833 participants having various cancer diagnoses. 193 of the participants included in these three studies were aged 80 years or more. Different generic and cancer-specific QoL instruments as well as different aims and outcomes were studied. All three studies used a diagnosis-specific instrument, but none of them used an age-specific instrument. Despite heterogeneity in cancer diagnoses, instruments used, and outcomes studied, QoL in home-dwelling cancer patients aged over 80 years old seems to be correlated with age, physical function, comorbidity, living alone, needing at-home care services, being in a poor financial situation and having a small social network. Conclusion: Our systematic review revealed only three studies exploring QoL and its determinants in the specific subgroup of home-dwelling cancer patients aged 80 years and over. A gap in the knowledge base has been identified. Future studies of this increasingly important and challenging patient group must be emphasized. Subgroup analyses by age must be performed, and valid age and diagnosis specific QoL instruments must be used to generate evidence in this segment of the population.