The aim of this study was to evaluate the clinical usefulness of the chromogranin A (CgA) determination in patients with neuroendocrine neoplasms (NENs) of the digestive system and to analyse the association between concentration of the marker and progression-free survival (PFS) and overall survival (OS). Serum concentrations of CgA were determined before the treatment in 131 patients with NENs, including patients with tumours located in the pancreas, the small intestine, caecum, appendix and in the colon. No significant associations were identified in CgA concentrations between the control group and patients with NENs in appendix and colon. In patients with NENs of the pancreas and NENs of the small intestine and caecum, increased CgA levels were associated with lymph node involvement, distant metastases and a baseline liver involvement. Analyses revealed significantly higher CgA concentrations in patients with active disease compared to those without symptoms of NEN. In patients with NENs of the pancreas, CgA concentration was correlated with tumour grade and Ki67. Significantly higher CgA levels were also found in patients who died compared to those who lived. Analyses of PFS and OS revealed that CgA concentration was not a prognostic factor in patients with NENs of the pancreas. In patients with NENs of the small intestine and caecum, increased CgA concentrations are independent, poor prognostic factors for both PFS and OS. In conclusion, in patients with NENs in pancreas, CgA levels are associated with disease progression, while in patients with NENs in small intestine and caecum, its concentration is a predictive indicator for PFS and OS.