We examined 4305 white newborn infants for 114 minor physical features and major malformations to evaluate the hypothesis that the presence of three or more minor anomalies is highly predictive of a major malformation. We confirmed that the infant with three or more minor anomalies is at increased risk for a major malformation. However, this risk (19.6%) was much lower than the risk of 90% popularized by Smith and based on the study of Marden et al. (J Pediatr 1964;64:357). Analysis of the findings in the two studies showed that the lower predictive value was probably related to differences in study design. Nevertheless, some minor anomalies remain essential to the early recognition of several serious malformation syndromes.