Two widely used quality of life questionnaires, European Organization for Research and Treatment of Cancer Core (EORTC QLQ-C30) & Functional Assessment of Cancer Therapy-General (FACT-G), were examined for their comparability using four different groups of cancer patients. During a follow-up investigation, 418 cancer patients (Hodgkin's disease, breast cancer, bone marrow transplantation (BMT), chronic lymphatic leukaemia (CLL)) completed both the EORTC QLC-C30 and the FACT-G during the same session. For an illustration of the differences between the two Quality of Life (QoL) instruments, pairs of diagnostic groups were formed and their QoL scores using the EORTC QLQ-C30 and FACT-G compared. The corresponding subscales of the EORTC-QLC-C30 and the FACT-G show only low to moderate intercorrelations across all four groups of cancer patients studied. In particular, a comparison of pairs, namely Hodgkin's disease versus breast cancer patients and BMT versus CLL patients, highlights substantial differences in the corresponding subscales of the EORTC QLQ-C30 and the FACT-G. The results of the QoL investigations should not be interpreted independently of the instrument used and an interpretation of results must be based on the contents of items of the respective questionnaires.