Biopsies of metastatic tissue are increasingly being performed. Bone is the most frequent site of metastasis in breast cancer patients, but bone remains technically challenging to biopsy. Difficulties with both tissue acquisition and techniques for analysis of hormone receptor status are well described. Bone biopsies can be carried out by either by standard posterior iliac crest bone marrow trephine/aspiration or CT-guided biopsy of a radiologically evident bone metastasis. The differential yield of these techniques is unknown. Results from three prospective studies of similar methodology were pooled. Patients underwent both an outpatient posterior iliac crest bone marrow trephine/aspiration and a CT-guided biopsy of a radiologically evident bone metastasis. Samples were assessed for the presence of malignant cells and where possible also for estrogen (ER) and progesterone receptor (PgR) expression. 40 patients were enrolled. Bone marrow aspiration/trephine biopsy was completed in 39/40 (97.5%) and CT-guided biopsy was completed in 34/40 (85%) of patients. Sufficient tumor cells for hormone receptor analysis were available in 19/39 (48.8%) and 16/34 (47%) of and bone marrow aspiration/trephine and CT-guided biopsies, respectively. Significant discordance in ER and PgR between the primary and the bone metastasis was also seen. Nine patients had tissue available from both bone marrow and CT-guided bone biopsies. ER and PgR concordance between these sites was 100 and 78%, respectively. Performing studies on human bone metastases is technically challenging, with relatively low yields regardless of technique. Given resource issues and similar success rates when comparing both techniques, bone marrow examination may be utilized first and if inadequate tissue is obtained, CT-guided biopsies can then be used.