Purpose <p>To evaluate the potential prognostic value of pretherapeutic Bone Marrow Scintigraphy (BMS) in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223 dichloride (Ra-223).</p> Methods <p>We analyzed 28 mCRPC patients who performed BMS and treated with Ra-223. Visual image analysis was performed and defined as follows: normal distribution (uptake in the vertebral column and bony pelvis) vs. medullary expansion (uptake at the distal half of femoral and/or humeral diaphysis or more distally). Correlation between medullary expansion status and baseline laboratory factors was performed. Survival analyses for evaluating the association between medullary expansion and other variables with overall survival (OS) were conducted using cox regression hazard model and Kaplan Meier methods.</p> Results <p>A total of 130 doses of Ra-223 were administered, with 17 (60%) patients received 6 cycles. BMS status was significantly correlated with hemoglobin levels (<i>p</i> &lt; 0.001), PSA levels (<i>p</i> = 0.008), the number of prior systemic therapies (<i>p</i> = 0.032) and radiotherapy (<i>p</i> = 0.01). Median OS was 19 months, with 16 patients dead. Among variables tested, BMS status, hemoglobin, number of therapies, and number of Ra-223 cycles were significantly associated with OS (hazard ratios: 3.3, <i>p</i> = 0.02; 0.75, <i>p</i> = 0.042; 1.74, <i>p</i> = 0.019; 4.6, <i>p</i> = 0.006; respectively). Patients with normal BMS had a median OS of 33 months vs. 7.6 months in those with medullary expansion (log-rank 5.5, <i>p</i> = 0.019).</p> Conclusion <p>This study demonstrated a significant association between medullary expansion status on BMS and OS in mCRPC patients treated with Ra-223. Patients exhibiting medullary expansion have worse outcomes compared to those without expansion. Medullary expansion was correlated with adverse prognostic biomarkers commonly linked to worse outcomes in mCRPC.</p>