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To determine the prenatal diagnostic accuracy of two-dimensional ultrasound (2DUS) alone versus 2DUS in conjunction with three-dimensional ultrasonography (3DUS) including orthogonal display (OGD) and three-dimensional extended Imaging for cleft lip and primary palate.Fetuses being suspected of having a facial cleft by previous ultrasound examination or family history were examined sequentially with 2DUS and then 3DUS.Of a total of 30 infants, 22 had cleft lip and nine also had cleft palate at birth. The use of 2DUS with or without 3DUS correctly identified all cases of cleft lips prenatally. However, the use of 2DUS in conjunction with 3DUS correctly identified more cleft primary palate than 2DUS alone (88.9% vs 22.2%, P < 0.01). Cleft primary palate was well demonstrated in both the multi-slice view (MSV)™ and OGD modes. In one case, a cleft palate was shown in the MSV™ mode but not in the Oblique view™ (OBV)™ mode. All the unaffected fetuses were reported as no cleft palate with the use of MSV™ mode.Combined approach of 2DUS and 3DUS with both OGD and MSV™ modes significantly improved the prenatal detection rate for a cleft palate compared with 2DUS alone (88.9% vs 22.2%) without decreasing the specificity.