['We compared the relationships of serum prostate specific antigen to tumor volume and to noncancerous prostate tissue volume using multivariate analysis in men undergoing prostatectomy during 2 periods.', 'From our prostatectomy database we randomly selected 200 men from 1991 to 1994 (early group) and 200 from 2000 to 2003 (recent group) who underwent radical prostatectomy without neoadjuvant therapy. The variables analyzed were patient age, log prostate specific antigen, pathological stage, Gleason score, log total tumor volume and log noncancerous prostate tissue volume. Univariate correlation and multiple regression analyses were performed to assess the linearity of the relationships among the variables.', 'There was a significant difference between the early and recent groups in age (median 64 years, IQR 58-67 vs 59, IQR 53-65; p<0.001), prostate specific antigen (8.3 ng/ml, IQR 5.7-12.5 vs 5.8, IQR 4.4-7.8; p<0.001), total tumor volume (2.0 cc, IQR 1.0-3.6 vs 1.4, IQR 0.6-2.9; p<0.001), Gleason score (7, IQR 7-8 vs 7, IQR 7-7; p<0.001) and the incidence of extraprostatic disease (39% vs 18.5%, p<0.001) but not in noncancerous prostate tissue volume (35.7 cc, IQR 28.6-46.5 vs 37.1, IQR 28.9-50.1). There was a relationship between log prostate specific antigen and log total tumor volume (r=0.486, p<0.001 and r=0.237, p<0.01), and between log prostate specific antigen and log noncancerous prostate tissue volume (r=0.179, p<0.05 and r=0.138, p=0.051) in the early and the recent groups, respectively. Multiple regression analyses revealed that log total tumor volume, log noncancerous prostate tissue volume and Gleason score were significant independent variables for predicting log prostate specific antigen in the 2 groups. In the recent group log noncancerous prostate tissue volume had the most significant association with log prostate specific antigen (p<0.001), whereas in the early group log total tumor volume had the most significant association (p<0.001).'] Does the relationship between serum prostate specific antigen level and tumor volume persist in the current era?