Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool to recognize cow's milk allergy (CMA) symptoms in infants. We aimed to assess the best cut-off point of CoMiSS in our country and investigate other parameters suggested to raise the strength of CoMiSS in CMA diagnosis. We enrolled 100 infants with CMA-suggestive symptoms with documentation of CoMiSS initially and 4 weeks after cow milk-free diet (CMFD) followed by an open food challenge (OFC) test. Infants with symptom recurrence upon challenge were diagnosed with confirmed CMA. Initial mean CoMiSS was 15.76 ± 5.29, being higher in the confirmed CMA group (84% of infants). Following CMFD, median CoMiSS significantly reduced to 1.5 in the confirmed CMA group compared to 6.5 in the negative group. Receiver operation characteristic (ROC) curve identified a CoMiSS score of ≥12 as the best cut-off value with 76.19% sensitivity, 62.50% specificity and overall accuracy of 74.00%. Mucoid stool, bloody stool and faltering growth were reported in 80, 41 and 52% of confirmed CMA infants, respectively, with considerable improvement following CMFD. Our study revealed a CoMiSS score of ≥12 to be the best cut-off point. However, CoMiSS cannot be used alone for accurate diagnosis of CMA. CoMiSS ≥12 can predict a positive response to CMFD; nevertheless, CoMiSS is a good awareness tool and cannot be regarded as a stand-alone CMA diagnostic test. CoMiSS reduction following CMFD was predictive of a reaction to OFC to diagnose CMA as well as for monitoring symptom improvement. Symptoms commonly associated with CMA as mucoid stool, bloody stool, marked abdominal distention not responding to medical treatment and faltering growth, in addition to their improvements in response to CMA are suggested parameters to be added to CoMiSS to improve its accuracy.