The aims of the study were to analyze the trends and characteristics of the incidence and clinical presentation of childhood celiac disease (CD) from 1976 to 2010 in Estonia. The study included all children up to 19 years of age diagnosed with small bowel biopsy proven CD. During a 35-year period, CD was diagnosed in 152 children in Estonia (68 boys, median age 2.3 years). From 1976 to 1980, the age-standardized incidence rate of CD was 0.10 per 100,000 person-years. After the introduction of gliadin and endomysium antibody screening (in conjunction with activities directed to increase the physicians awareness), the incidence rate increased from 0.48 in 1986-1990 to 1.55 per 100,000 person-years in 1991-1995. After initiating screening with anti-tissue transglutaminase antibodies in 2003 and routine screening for CD among all children with newly diagnosed type 1 diabetes in 2005, the incidence rate increased from 1.59 in 2001-2005 to 3.14 per 100,000 person-years in 2006-2010 (median age 6.8 years). Our nationwide study demonstrates a more than 30-fold increase in the incidence of childhood CD over a 35-year period in Estonia, along with changing patterns in the presentation of pediatric CD. In addition to the impact of use of novel CD screening methods, active search and rising of the awareness among doctors may have strongest effect. Both environmental and social factors could be also involved in the increase in CD incidence.