Congenital defects in the intestinal mucosa can provoke diarrhea in the neonatal period. This kind of diarrhea is difficult to treat and the outcome is bad if intestinal transplantation is not done. We describe the case of newborn female with severe protracted secretory diarrhea, which started after first oral intake of breast milk. The newborn presented with severe dehydration and persistent metabolic acidosis though potential treatment was not stopped. Endoscopy with the biopsies from the distal part of duodenum mucosa was done on the third week of life. Histological examination revealed the pathological mucosa with the total microvillous atrophy, surface epithelium thinning and histochemical PAS (Periodic acid-Schiff reaction) positivity of enterocytes apical region. These changes are typical for rare microvillous inclusion disease. When the diagnosis of microvillous inclusion disease is made, the only treatment is total parenteral nutrition and intestinal transplantation.