PURPOSE: To compare prospectively the diagnostic performance of radiologists who used conventional ultrasonography (US) with that of radiologists who used spatial compound imaging for the differentiation of benign from malignant solid breast masses. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained. Before excisional or needle biopsy was performed, conventional US and spatial compound images were obtained in 67 patients (age range, 25-67 years; mean age, 45 years) with 75 solid breast masses (21 cancers and 54 benign lesions). Three experienced radiologists who did not perform the examinations independently analyzed US findings and indicated the probability of malignancy. Results were evaluated with κ statistics and receiver operating characteristic (ROC) analysis. RESULTS: For US findings, the presence of calcifications was the most discordant feature (κ = 0.372) between conventional US and spatial compound imaging, followed by echotexture (κ = 0.439), boundary echo (κ = 0.496), orientation (κ = 0.518), echogenicity (κ = 0.523), shape (κ = 0.526), margin (κ = 0.569), and posterior acoustic transmission (κ = 0.669). The area under the ROC curve for conventional US was 0.79 for reader 1, 0.88 for reader 2, and 0.82 for reader 3, and the area under the ROC curve for spatial compound imaging was 0.85 for reader 1, 0.88 for reader 2, and 0.89 for reader 3. The partial area index for conventional US was 0.29 for reader 1, 0.69 for reader 2, and 0.39 for reader 3, and the partial area index for spatial compound imaging was 0.29 for reader 1, 0.65 for reader 2, and 0.39 for reader 3. The difference between the diagnostic performances of the two techniques was not significant (P > .05). CONCLUSION: The performance of the radiologists with respect to the characterization of solid breast masses was not significantly improved with spatial compound imaging. © RSNA, 2005.