- Objectives To correlate the findings of prostate color Doppler sonography (CDS) with those of site-specific transrectal ultrasound-guided core biopsy; to evaluate the significance of two different color presets in detecting prostate cancer compared with gray-scale transrectal ultrasonography; and to compare the accuracy of conventional gray-scale transrectal ultrasound (CGS)-guided biopsy with CDS-guided biopsy. Methods Seventy patients were enrolled in this prospective study. CDS was performed before biopsy. Two color presets were used: CDS-1 (high sensitivity) and CDS-2 (high specificity). The color flow was graded on a scale from 0 to 2+. At the completion of the color grading, color maps were constructed. In each case, CDS-guided biopsy was performed followed by CGS-guided biopsy (six sextant biopsies and focal lesional biopsies). Results The cancer detection rate was 33%, 31%, and 27% for CGS-guided biopsy, CDS-1, and CDS-2, respectively. CDS-1 was more sensitive than CDS-2 (81% versus 60%) but both presets had similar specificities (79% versus 82%). CGS-guided biopsy yielded a sensitivity of 90%, a specificity of 38%, and a positive and negative predictive value of 34% and 83%, respectively. A biopsy strategy combining hypoechoicity with increased color flow increased the specificity to 97%, positive predictive value to 68%, and negative predictive value to 84%, but its sensitivity was low (18%). Conclusions Our experience suggests that low-velocity, high-sensitivity color is superior to all other CDS settings. The presence of focal peripheral zone hypervascularity at CDS is associated with a high likelihood of prostate cancer. However, only a combination of CDS guidance with six sextant biopsies may achieve maximal sensitivity and specificity.