Abstract Introduction Lactose intolerance is the failure to digest foods and beverages containing the lactose present in milk. Lactose intolerance can be presented by many digestive symptoms. Objective To validate the modified CoMiSS score for the prediction of lactose intolerance, that was confirmed by a stool acidity test. Patients and Methods A crosssectional study, conducted on Ain Shams University Hospitals/ Gastrointestinal Clinics, enrolled100 adult participants during the period from December 2018 to December 2019, with the presence of one or more gastrointestinal symptoms, and subjected to a stool acidity test as a reference test and modified CoMiSS as index test. Results The mean age of participants was 35.30 ± 10.714 years old; 55% were females, and mean BMI was 23.08 ± 2.080 kg/m2, with no statistically significant difference between lactose intolerance and patients gender or body mass index BMI, 24% of participants had positive stool PH, lactose Intolerance diagnosed according to modified CoMISS Score among 19% of study participants, the mean of modified CoMISS Score in positive cases (12.37) were highly statistically significant than those negative lactose intolerance (2.33) as p < 0.001, Area under ROC Curve was 0.998, with cut-off value >8. Sensitivity 89.5% and specificity was 100%. Conclusion Modified CoMiSS is a simple, fast, and easy-to-use tool that can predict lactose intolerance, with a cut-off value of > 8, the Area under the ROC Curve was 0.998, sensitivity 89.5%, and specificity was 100%.