Diagnosis of Crohn's disease is usually made at a symptomatic stage. However diagnosis at a pre-clinical stage might provide valuable information on etiology/pathogenesis and allow early intervention to alter its natural history. We describe here the case of a 27 year old woman who was diagnosed with Crohn's disease at a completely asymptomatic stage and followed up for more than six years. She was part of an ongoing screening study in first degree relatives of Crohn's disease patients. At diagnosis, colonoscopy showed modest inflammation and few superficial ulcerations and erosions in the ileo-cecal valve and the terminal ileum. Fecal calprotectin was only modestly elevated. Intestinal permeability was also increased. During follow-up and while still asymptomatic the patient was sequentially treated with therapeutic doses of 5-ASA, budesonide, azathioprine and infliximab in an attempt to stop disease progression. Only infliximab appeared capable of inducing profound mucosal healing—however the disease recurred several months after the medication was ceased. Over time, quantification by immunohistochemistry of a number of cell types and cytokines revealed a positive correlation between CD4-CD25-FOXP3 (Treg) cell number and inflammation, a finding potentially consistent with tissue resistance to Tregs' activity.