The cutoff value of critical weight loss is still subject of discussion. In this pilot study, we investigated whether ≥ 5% weight loss in the past year predicts changes in nutritional status in patients with advanced cancer during treatment with palliative chemotherapy. In 20 patients with advanced cancer undergoing palliative (combination) chemotherapy, body weight, fat free mass (FFM), and cachexia were measured prior to the start and at 9 wk of treatment. History of weight loss was used to test differences in development of nutritional parameters during chemotherapy with use of independent sample t-tests. At baseline, 10 of 20 patients had lost ≥ 5% body weight during the past year and 5 patients were cachectic. The change in FFM in the first 9 wk of chemotherapy was significantly worse in patients with ≥ 5% weight loss compared to patients with <5% weight loss [mean difference: 3.5 kg (P = 0.001)]. Data also suggest that ≥ 5% weight loss predicts shorter survival (P = 0.03). We found that patients with ≥ 5% weight loss prior to chemotherapy have a deterioration in nutritional status during chemotherapy and may have a shorter survival. These results have to be confirmed in a larger study including a robust survival analysis.