We analyzed 115 iliac crest bone marrow biopsy specimens from 101 patients with metastatic castration resistant prostate cancer, divided into a test (n = 57) and a validation (n = 58) set. We developed a score based on computed tomography Hounsfield units and lactate dehydrogenase levels, which were associated with a positive biopsy result. The score can be used to select patients for whom a bone marrow biopsy will provide tissue for molecular characterization. Background: The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of clinical and imaging criteria could maximize tissue acquisition from bone marrow biopsies (BMBs). We aimed to develop a score for the selection of patients undergoing BMB. Materials and Methods: A total of 115 BMBs were performed in 101 patients: 57 were included in a derivation set and 58 were used as the validation set. The clinical and laboratory data and prebiopsy computed tomography parameters (Hounsfield units [HUs]) were determined. A score for the prediction of biopsy positivity was developed from logistic regression analysis of the derivation set and tested in the validation set. Results: Of the 115 biopsy specimens, 75 (62.5%) were positive; 35 (61.4%) in the test set and 40 (69%) in the validation set. On univariable analysis, hemoglobin (P = .019), lactate dehydrogenase (P = .003), prostate specific antigen (P = .005), and mean HUs (P = .004) were selected. A score based on the LDH level (>= 225 IU/L) and mean HUs (>= 125) was developed in multivariate analysis and was associated with BMB positivity in the validation set (odds ratio, 5.1; 95% confidence interval, 1.9%-13.4%; P = .001). The area under the curve of the score was 0.79 in the test set and 0.77 in the validation set. Conclusion: BMB of the iliac crest is a feasible technique for obtaining tumor tissue for genomic analysis in patients with castration-resistant prostate cancer metastatic to the bone. A signature based on the mean HUs and LDH level can predict a positive yield with acceptable internal validity. Prospective studies of independent cohorts are needed to establish the external validity of the score. (C) 2016 The Author(s). Published by Elsevier Inc.