The objective of this study was to assess the incidence of circulating tumor cells (CTCs) in prostate cancer patients with low-volume tumors (less than 0.5 cc) after radical prostatectomy (RP). Blood samples were collected from 64 RP patients to assess the incidence of CTCs following RP. The specimens were processed by whole-mount section. Clinicopathological data (e.g. patient age, race, specimen weight, tumor volume, grade, stage and surgical margin status) and follow-up PSA data were compared to CTC status. Of the 64 RP patients, nine had 'low-volume prostate cancer'. Seven of these patients had detectable levels of CTCs. In two of the seven patients with detectable CTCs, PSA elevation was also observed. Isolation and detection of circulating epithelial cells is possible in low-volume prostate cancer patients. In the setting of low-volume prostate cancer, CTCs may be associated with the presence of detectable PSA levels. However, the detection of CTCs did not predict PSA failure.