The objective of this paper is to validate prostate specific antigen (PSA) density (PSAD) routine use to enhance PSA specificity in men with normal digital rectal examination and intermediate PSA values. It is a retrospective study of 235 men from a prostate cancer (PCa) screening program. All of them presented PSA values between 4 and 10 ng/ml, normal digital rectal examination, and a transrectal ultrasound (TRUS) guided biopsy available (PSA>/=4 ng/ml as the sole criterion for biopsy). Multivariate analysis failed to demonstrate higher PSAD values in men with PCa. PSAD cutoff points higher than 0.07 ng/ml per cc were considered as unacceptable, with less than 95% sensitivity. When a cutoff point of 0.15 was considered, as many as 30.6% of the cancers were missed. In conclusion we cannot recommend the use of this parameter for the above mentioned purpose.Prostate Cancer and Prostatic Diseases (2001) 4, 146-149.