BACKGROUND: Multiple causes of false-positive chromogranin A (CgA) measurement have been reported that may affect its impact as a surrogate marker of RECIST progression in well-differentiated gastroenteropancreatic neuroendocrine tumors (WDGEPNET). ? AIMS: 1) To evaluate the frequency of false-positive CgA results. 2) To prospectively compare CgA variations with RECIST morphological changes in patients without known causes of false-positive CgA measurements.? METHODS: First, the conditions responsible for potentially false-positive CgA measurements were screened in 184 consecutive patients with metastatic WDGEPNET. Secondly, a variation in CgA at a 6-month interval was compared to RECIST results at 6 months in 46 patients.? RESULTS: Among 184 patients, elevated CgA was found in 130 cases (71%) including 99 patients with at least one cause of a false-positive result. Impaired kidney function as well as medication with proton pump inhibitors were found to be the 2 major causes of false-positive results. The sensitivity and specificity of CgA measurements compared with morphological tumor changes according to the RECIST criteria were 71% and 50%, respectively, at 6 months.? CONCLUSION: Routine screening for the causes of false-positive CgA measurements is mandatory in WDGEPNET patients. Our study does not validate the use of CgA as a surrogate marker of tumor progression.