Short-term fasting (STF) has been shown to protect healthy cells against the adverse effects of chemotherapy while making tumor cells more vulnerable to it. The present randomised pilot cross-over study was designed to assess the effect of a 60 hour STF on quality of life (QOL), well-being and fatigue in patients with gynaecological cancer undergoing chemotherapy. Group A was randomised to a STF during the first three of six scheduled chemotherapies (36 h before to 24 h after the chemotherapy) followed by non-calorie restricted nutrition during the following three chemotherapies. During the fasting period subjects received unrestricted amounts of water, herbal tea, 2x100cl vegetable juice and small standardized quantities of light vegetable broth with a maximum total daily energy intake of 350 kcal. Group B was allocated to a vice versa sequence of nutrition. All measurements were performed at baseline and eight days after each chemotherapy cycle. A variety of questionnaires were used for assessment of QOL, general well-being and fatigue. 34 patients with breast or ovarian cancer completed the study. Fasting was safe and all reported side effects were of low grade. STF led to a better tolerance to chemotherapy with less compromised QOL and reduced fatigue within the 8 days after chemotherapy. At the final consultation the majority of patients reported better tolerance to chemotherapy with STF. The authors conclude that STF during chemotherapy is feasible and has beneficial effects on QOL, well-being and fatigue.