Introduction: The measurement of quality of life is an increasingly important issue, particularly in regard to treatment of severe and chronic diseases. The aim of this pilot study was to assess potentially divergent profiles of quality of life in persons with two different pathologies: moderate dementia and cancer. Method: This pilot study was carried out in the neurology and cancer services of the medical school in Montpellier, France (Hôpital Gui de Chaulliac and CRLC Val d'Aurelle). The cumulative self-reporting test WHOQOL 100 (World Health Organization Quality of Life with 100 questions) was administered in 57 patients with either moderate senile dementia (27 cases with a Mini-Mental State Examination score > 15; mean age of 73) or cancer (30 cases, mainly women with breast cancer; mean age of 53). The stability of responses was tested in a 2-week period. Results: Results of the study showed clear and significant differences between the two groups in the domains of mobility and psychology. Further, eight questions and six facets with a significant difference in responses were found. Responses seemed more stable in the domains of autonomy, social relationship, and religion for the cancer group, and in autonomy and psychology for the dementia group. The age difference may be an important factor in the different quality of life measured but did not significantly influence responses to the test questions. Conclusion: The WHOQOL 100 seems a powerful instrument to assess quality of life in diseases such as cancer and moderate dementia. In this study, interesting differences in responses to the test questions between the two pathologic conditions were identified. Items that were unreliable on retesting are singled out. These results will be applied and reevaluated in the development of future, illness-specific and shorter versions of the WHOQOL 100.