Surgicalhe activity of nucleolar organizer regions (NORs) in chromosomes of peripheral blood lymphocyte cultures from 20 healthy subjects and 32 patients with celiac disease (CD) (nine untreated patients, nine treated but with dietary lapses, and 14 treated with gluten-free diet (GFD) and normal small bowel histology) was studied. Furthermore, three female patients diagnosed with small bowel non-Hodgkin's lymphoma (NHL) complicating CD were studied. Silver (Ag)-staining technique was used to visualize positive NORs. In each individual, 20 metaphases were analyzed to determine the number of NORs per cell. The average of Ag-NOR+ per cell, expressed as X ± SD, was found to be higher in the CD group (6.62 ± 0.65) compared with controls (5.70 ± 0.81) (p < 0.001). This increase was evident in both groups of chromosomes analyzed (D and G). No differences were found among the three groups, but all of them were found to be statistically different compared to controls (p < 0.001). The NHL complicating CD patients showed a statistically increased frequency of Ag-NORs (7.20 ± 0.39) with respect to CD patients (p < 0.02) and controls (p < 0.001). These findings show an increase of the transcriptional activity of rDNA in CD that could be related to the high incidence of malignancy in this pathology. Longitudinal studies of CD patients should be performed to confirm this evidence.