Neuroendocrine tumours (NETs) are rare tumours that originate from neuroendocrine cells and their incidence has increased for the last 20 decades; partly because of advances in diagnostic tools, which have improved detection rates. Chromogranin A (CgA) is the most widely used biochemical tumour marker for NETs, however, its prognostic utility has been questioned due to several non-neuroendocrine causes of elevated CgA. This is the first study to assess the prognostic utility of chromogranin B (CgB), a marker of NET that is less affected by these clinical drawbacks. As a result, we hypothesised that plasma CgB concentration is a more accurate and reliable prognostic indicator in NET patients. Data from 121 NET patients were collected retrospectively and submitted to statistical analyses. In univariate survival analysis, circulating CgB levels were associated with a significantly poorer survival time than CgA. In addition, multivariate analysis was performed by considering other prognostic indicators, including age, metastases at diagnosis; and, nonetheless, an elevated circulating CgB concentration was the most significant predictor of poor survival. Further comparisons of chromogranins with different measures of tumour burden demonstrated that plasma CgB levels were associated with a significant increased risk of disease progression. In conclusion, results show that CgB allows a more accurate distinction of patients with an increased risk of death and tumour progression in NET patients.