Circulating Chromogranin A (CgA), total PSA (TPSA) and F-PSA concentrations were measured in 211 patients (pt) with newly diagnosed prostate cancer (PC) and in 25 controls with benign prostatic hypertrophy (BPH). TPSA values ranging 3.5-5.5 ng/ml were found in 14 PC pt (6.6%), 5.5-9.9 ng/ml in 29 pt (13.7%), 10-19.9 ng/ml in 75 pt (35.6%), 20-50 ng/ml in 64 pt (30.3%) and > 50 ng/ml in 29 pt (13.7%). In those groups of PC pt false negative % F-PSA level > 18 was respectively measured in 0 out of 14, 2 out of 29 (6.9%) 6 out of 75 (8.0%), 61 out of 4 (9.4%) and 6 out of 29 (20.7%) pt, or totally in 20 out of 211 (9.5%) pt. Among 20 PC pt with false negative %F-PSA data elevated CgA level (> 80 ng/ml) was found in 18 subjects (18 out of 20 90%) or respectively in 0, 1/2 (50%), 516 (83%), 6 out of 6 (100%) and 6 out of 6 (100%) patients. Bone scintigraphy was performed in all pt with TPSA concentration > 10 ng/ml at the time of diagnosis. Bone lesions were respectively found in 4 out of 75 (5.3%) pt with TPSA 10-20 ng/ml, 12 out of 64 (14%) pt with TPSA level from 20-50 mg/ml and in 25k9 (75.9%) pt with. TPSA above 50 ng/ml. Overall osseous metastases were recorded in 41 out of 211 pt (19.4%) with newly diagnosed PC and in 18 of these Stage D2 pt (43.9%) elevated CgA concentration were measured Among them elevated CgA level and tumor dissemination matched with false negative %F-PSA parameter (> 18%) in 4 out of 18 (22.2%) pt as well as in 37 out of 191 (19.4%) pt with %F-PSA < 18% (p > > 0.05). In parallel, a positive CgA level in newly presented PC pt was closely associated with %F-PSA false negativity (18 out of 20, 90%). A negative correlation between TPSA elevation and the magnitude of CgA serotest level indicate differences in their biological origin and activities. According to the data reported herein we advocate the assessment of serum Chromogranin A concentration in first presented patients with clinically proven PC, elevated T-PSA level and %F-PSA parameter > 18%. Neuroendocrine structures are resistant toward hormonal treatment and hence CgA measurement is strongly suggested in all candidates for a systemic hormone therapy.