Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H 2 -BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T 213 910 has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T 213 910 and lactose H 2 -BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17-79 years, and 55 males, mean age 38, range 18 -68 years) patients with clinical suspicion of LD underwent a 3 -4 h H 2 -BT and genetic testing for LCT C/T 213 910 . Patients rated five intestinal and four extra-intestinal symptoms during the H 2 -BT and then at home for the following 48 h. Declaring H 2 -BT as the gold standard, the CC 213 910 genotype had a sensitivity of 97 % and a specificity of 95 % with a k of 0·9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H 2 -BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H 2 -BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD. Worldwide, over 5 billion humans are estimated to suffer from lactase (LCT) deficiency, which is the most common cause of lactose intolerance. The geographical distribution of lactose intolerance is variable depending mostly on heritage: in Asian countries, close to 100 % of the general population is considered lactose intolerant, whereas in Northern Europe, prevalence reaches about 10 -20 % increasing towards the south (1) . Lactose is a disaccharide physiologically cleaved into glucose and galactose by LCT located on the luminal membrane of the enterocytes located in the proximal small bowel. Reduced expression and/or activity of LCT leads to an accelerated intestinal transit and degradation of lactose by colonic bacteria into SCFA, H 2 and other metabolites implicated in the pathophysiology of classical abdominal symptoms such as diarrhoea, bloating, borborygmi and abdominal pain. Most laboratories employ a lactose H 2 -breath test (H 2 -BT) in diagnosing LCT deficiency (LD). This test exploits the fact that H 2 , a by-product of bacterial lactose metabolism, is absorbed through the intestinal mucosa into the venous blood, and transported past the liver into the alveoli of the lungs, from where it is exhaled (2,...