In attempting to give more years of life to cancer patients, their Quality of Life (QoL) during this time has frequently been compromised. Assessment of patients’ QoL provide nurses with an opportunity to know about the whole range of patients’ needs and desires. These information would be potentially very useful for health care professionals particularly nurses for planning, conducting and evaluating the nursing care of cancer patients. Questionnaire survey research carried out in countries other than Australia identified a varied amount of agreement between cancer patients and nurses about cancer patients’ QoL. However, based on the literature review, no research study has been found in Australia that provides a detailed understanding of how nurses and cancer patients are similar or different in their perceptions of cancer patients’ QoL. A research study, therefore, was conducted to answer the following key questions: (a) what differences and/or similarities are there between patients’ and nurses’ perceptions of cancer patients’ QoL; (b) why do these differences and/or similarities exist? A research study with a mixed approach was undertaken to answer the research questions. In the first phase, a survey by questionnaire was conducted. The main aims were to identify: (a) the level of agreement between cancer patients’ and nurses’ scores on the World Health Organisation’s Quality of Life Brief questionnaire (WHOQoL-BREF); and (b) variables that may influence the level of agreement between them. Each patient and nurse was invited to complete the WHOQoL-BREF questionnaire, which was considered as an appropriate tool for evaluating cancer patients’ QoL. This questionnaire considers QoL across four domains or dimensions: physical, psychological, social relationship and environmental. In the first phase of the study, 166 cancer patients and 95 nurses were recruited from three major hospitals in Adelaide, South Australia. The patients had a range of cancer diagnoses with breast cancer being the most prevalent. Most patients were being treated as inpatients with chemotherapy being their primary treatment. The mean age of nurses was approximately 37 years and their clinical experience with cancer patients averaged approximately eight years. Intraclass Correlation Coefficient (ICC) between patients’ and nurses’ scores ranged from ‘poor’ in the social relationship and psychological domains up to ‘moderate’ in the physical domain indicating that generally nurses were different in their perceptions from those of cancer patients. Another major finding of this phase was that nurses underestimated cancer patients’ QoL in the social relationship and environmental aspects, which consisted of more personal and private issues. Having finished the first phase, the second phase was conducted based on the principles of a classical version or mode of grounded theory. The aim here was to include an interpretive perspective and explore the reasons why nurses may differ in their perceptions about cancer patients’ QoL in comparison to cancer patients. In this phase, three cancer patients and 10 nurses took part in semi-structured interviews. Participants were selected from different inpatient and outpatient oncology services and a palliative setting. Differences in patients’ and nurses’ perceptions about cancer patients’ QoL and their implications for nursing clinical practice were discussed further in the light of six important categories found in the second phase including: QoL meanings, QoL aspects, Cues-based QoL assessment; Purpose-based QoL assessment; Facilitators of QoL assessment; and Barriers to QoL assessment. It emerged that QoL has individualised meanings and nurses generally have difficulties understanding their patients’ personal perspective or definition of QoL. Another interpretive outcome that may explain why nurses differed in their perceptions when compared with cancer patients is that nurses’ assessment of cancer patients’ QoL in oncology wards is mainly made during their interaction with patients when providing care. Such an assessment has a focus on physical cues and may not facilitate nurses developing a more holistic picture of cancer patients’ QoL. Participants in the interpretive phase indicated that time limitations, focus on care tasks, and discontinuity of care, all work against nurses developing a more accurate understanding of cancer patients’ QoL. Conversely, it was found that building a relationship and stronger rapport with patients is the main facilitator in improving nurses’ understanding of cancer patients’ QoL.