The purpose of this study was to explore whether detection of disseminated tumor cells (DTCs) in bone marrow (BM) of nonmetastatic prostate cancer (PC) was associated with other clinical or histopathological factors at diagnoses or clinical outcome subsequent to definitive radiotherapy (RT). We evaluated BM aspirates from 272 cT1-4pN0M0 PC patients by immunocytochemistry employing anticytokeratin antibodies (AE1/AE3). BM-status was compared with clinical and histopathological parameters. Long-term clinical outcome was assessed in 131 of the patients who all had completed definitive RT with or without androgen deprivation (AD), initiating treatment >5 years before cut-off date June 1, 2005. They had at least 1 unfavorable prognostic feature defined as cT3-4 or Gleason score (GS) ≥ 7B or PSA ≥ 10 μg/l. Overall death, cause-specific death, distant metastases (DM) as first clinical relapse, local failure as first clinical relapse and biochemical failure were defined as end-points. DTCs were detected in 18% of the patients and were associated with increasing GS (p = 0.04) and percentage of Gleason pattern 4/5 (p = 0.04). The 7-year cumulative risk of DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p = 0.07). In patients receiving RT without AD (n = 75), the 7-year cumulative risk of DM for BM-positive patients was 28% vs. 9% for BM-negative patients (p = 0.03). BM-status did not have impact on other end-points. In conclusion our study shows that presence of DTCs in BM at diagnosis was associated with the histological differentiation of the primary tumor and an increased risk of developing distant metastases after RT. © 2007 Wiley-Liss, Inc.