Prostate adenocarcinomas (PAC) consist mainly of tumour cells of luminal immunophenotype and scattered neuroendocrine (NE) cells. NE cells are defined by chromogranin A (CgA) immunoreactivity. T he aim of this study is the evaluation of CgA serum levels in monitoring prostate cancer (PC) patients under complete androgen deprivation (CAD) in comparison with the prostate specific antigen (PSA) as a prognostic marker of androgen resistance and bone metastases. Ninety-two patients with newly diagnosed PAC and 30 healthy blood donors serving as the control group were enrolled in the study. Serum CgA and PSA values were measured. All patients had locally advanced or metastatic disease and received CAD treatment. In the group of PAC patients bone scanning with 925MBq (99m)Tc-MDP revealed the presence of bone metastatic lesions in 50 patients (29 with more than 3 lesions and 21 with less than 3 lesions). The other 42 patients had no bone metastases. The patients and the control group were re-evaluated after 1 year. Our results showed that serum CgA positively correlated with multiple bone metastases and higher Gleason score, serum levels of CgA and PSA. Levels of PSA were significantly higher in patients with PAC and bone metastases compared with those with no bone metastases (P<0.001). In patients with multiple bone metastases and Gleason Score >7 elevated serum levels of CgA higher than those of PSA were found. In conclusion, serum CgA levels is a valuable marker for predicting the presence of multiple bone metastases in PAC patients. Combined with PSA, CgA can predict disease progression in patients with advanced PAC under CAND treatment and is correlated with poor prognosis.