This　study　aimed　to　assess　the　utility　of　second-look　ultrasonography　(US)　in　differentiating　breast　imaging　reporting　and　data　system　(BI-RADS)　4　calcifications　initially　detected　on　mammography　(MG).　BI-RADS　4　calcifications　have　a　wide　range　of　positive　predictive　values.　We　hypothesized　that　second-look　US　would　help　distinguish　BI-RADS　4　calcifications　without　clinical　manifestations　and　other　abnormalities　on　MG.　This　study　included　1622　pure　BI-RADS　4　calcifications　in　1510　women　(112　patients　with　bilateral　calcifications).　The　cases　were　randomly　divided　into　training　(85%)　and　testing　(15%)　datasets.　Two　nomograms　were　developed　to　differentiate　BI-RADS　4　calcifications　in　the　training　dataset:　the　MG-US　nomogram,　based　on　multifactorial　logistic　regression　and　incorporated　clinical　information,　MG,　and　second-look　US　characteristics,　and　the　MG　nomogram,　based　on　clinical　information　and　mammographic　characteristics.　Calibration　of　the　MG-US　nomogram　was　performed　using　calibration　curves.　The　discriminative　ability　and　clinical　utility　of　both　nomograms　were　compared　using　the　area　under　the　receiver　operating　characteristic　curve　(AUC)　and　the　decision　analysis　curve　(DCA)　in　the　test　dataset.　The　clinical　information　and　imaging　characteristics　were　comparable　between　the　training　and　test　datasets.　The　bias-corrected　calibration　curves　of　the　MG-US　nomogram　closely　approximate　the　ideal　line　for　both　datasets.　In　the　test　dataset,　the　MG-US　nomogram　exhibited　a　higher　AUC　than　the　MG　nomogram　(0.899　vs　0.852,　P = .01).　DCA　demonstrated　the　superiority　of　the　MG-US　nomogram　over　the　MG　nomogram.　Second-look　US　features,　including　ultrasonic　calcifications,　lesions,　and　moderate　or　marked　color　flow,　were　valuable　for　distinguishing　BI-RADS　4　calcifications　without　clinical　manifestations　and　other　abnormalities　on　MG.　©　2024　Lippincott　Williams　and　Wilkins.　All　rights　reserved.