Celiac disease is a common cause of malabsorption in western countries, with significant geographic variation in incidence. Recent epidemiological studies using serology tests, however, suggest that the disease is more common than previously realized and homogeneously distributed in Europe. These studies have also demonstrated that the clinical presentation of the disease may greatly vary even between neighboring countries. Celiac disease remains a rare diagnosis in the United States. Whether the disease is underdiagnosed or is truly rare remains to be established. We have conducted preliminary studies, both on pediatric patients and adult blood donors, that seem to suggest that the prevalence of positive screening tests for celiac disease in the USA is equivalent to that reported in similar screening studies conducted in Europe. These data also suggest that the dimensions of the American celiac disease iceberg seem to be similar to those of the European one. The visible tip of the American iceberg, however, appears to be much smaller, since most of it still remains submerged. The reasons for these divergences remain unknown and may only be partially related to the limited attention to the disease by the American scientific community. Large, multicenter serological screening studies are needed to define the true prevalence of celiac disease in the United States.