Cow's milk is one of the first foods introduced to infants, and it can cause adverse reactions due to its various components and different pathophysiologies. Lactose intolerance (LI) and cow's milk allergy (CMA) are the most common adverse reactions to cow's milk. LI is due to insufficient small intestinal lactase activity or a large quantity of ingested lactose, leading to gastrointestinal symptoms such as abdominal pain, flatulence, and diarrhea. CMA, on the other hand, is an immune-mediated reaction to cow's milk proteins, particularly casein or β-lactoglobulin, and can affect multiple organ systems, including the skin, gastrointestinal tract, and respiratory system. The clinical manifestations of LI and CMA are similar, which can lead to misdiagnosis or delayed diagnosis, as well as nutritional risks due to inappropriate dietary interventions. The article aims to assist clinicians in understanding the pathophysiology of LI and CMA and recognizing the similarities and differences in their clinical manifestations. Formula-fed infants with LI should be treated with formula containing reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow's milk protein or amino acids. The article also discusses the diagnostic approaches and management strategies for both conditions, emphasizing the importance of accurate diagnosis to ensure appropriate dietary interventions.Cow's milk is one of the first foods introduced to infants, and it can cause adverse reactions due to its various components and different pathophysiologies. Lactose intolerance (LI) and cow's milk allergy (CMA) are the most common adverse reactions to cow's milk. LI is due to insufficient small intestinal lactase activity or a large quantity of ingested lactose, leading to gastrointestinal symptoms such as abdominal pain, flatulence, and diarrhea. CMA, on the other hand, is an immune-mediated reaction to cow's milk proteins, particularly casein or β-lactoglobulin, and can affect multiple organ systems, including the skin, gastrointestinal tract, and respiratory system. The clinical manifestations of LI and CMA are similar, which can lead to misdiagnosis or delayed diagnosis, as well as nutritional risks due to inappropriate dietary interventions. The article aims to assist clinicians in understanding the pathophysiology of LI and CMA and recognizing the similarities and differences in their clinical manifestations. Formula-fed infants with LI should be treated with formula containing reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow's milk protein or amino acids. The article also discusses the diagnostic approaches and management strategies for both conditions, emphasizing the importance of accurate diagnosis to ensure appropriate dietary interventions.