Greater understanding of factors contributing to nutritional deterioration in cancer, as well as patients expectations and the personal disease impact, are required to devise meaningful nutritional therapy. In a cross-sectional study of 205 patients with cancer of the head-neck, oesophagus, stomach, colon/rectum, nutritional deterioration was multifactorial and mainly determined by the tumour burden. In a larger cohort of 271 patients, although cancer stage and location were the major determinants of the patients Quality of Life, nutritional deterioration combined with deficiencies in nutritional intake were functionally more relevant than cancer stage. Based on this framework, we tested the potential role of nutritional intervention on patient predefined outcomes: nutritional status, diet intake, morbidity and Quality of Life. Two prospective randomised controlled trials were conducted in patients with cancer of the colon/rectum (n=111) or head-neck (n=75), in both instances patients were stratified for staging. In order to compare nutritional interventions during radiotherapy, each study had 3 arms: intensive dietary counselling vs oral supplements vs ad libitum intake; outcomes were analysed at the end and 3 months after radiotherapy, the latter period without intervention. In both trials, only nutritional interventions positively influenced outcomes during radiotherapy; 3 months after its completion, intensive counselling was the single method capable of sustaining a significant impact on patients outcomes. Nutrition is central to the improvement of a diversity of patient outcomes in colorectal and head-neck cancer patients.